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Petraikin, Pickhardt, Belyaev, Belaya, Pisov, Bukharaev, Zakharov, Kudryavtsev, Bobrovskaya, Semenov, Akhmad, Artyukova, Abuladze, Nizovtsova, Blokhin, Vladzymyrskyy, and Vasilev: Opportunistic screening for osteoporosis using artificial intelligence-based morphometric analysis of chest computed tomography images: a retrospective multi-center study in Russia leveraging the COVID-19 pandemic

Abstract

Study Design

Retrospective cohort study.

Purpose

To evaluate the effectiveness of opportunistic osteoporosis screening using an artificial intelligence (AI) algorithm for detecting vertebral compression deformity (VCD >25%) and reduced bone mineral density (BMD) from routine chest computed tomography (CT) scans.

Overview of Literature

Osteoporosis is an insidious metabolic disease that often remains asymptomatic for a long time, and is typically diagnosed due to the occurrence of complications. An approach for diagnosing osteoporosis based on routine CT examinations, including the use of AI services, is being actively studied.

Methods

Patients aged >50 years who underwent chest CT using the standard protocol between 09.06.2021 and 30.06.2021 at four inpatient and three outpatient clinics were retrospectively enrolled. The morphometric AI algorithm detected vertebral compression index and vertebrae density in Hounsfield units (HU). The AI algorithm was calibrated for BMD measurements using a phantom. Osteoporotic BMD was defined according to the American College of Radiology criteria (<80 mg/mL). The presence of vertebral fracture (VF) was verified using semiquantitative and algorithm-based qualitative methods by three radiologists, followed by two experts with 15 and 35 years of experience in the field.

Results

CT studies of 1,888 patients (mean age, 66.3 years) were included. The AI algorithm detected VCD in 336 patients (17.8%), with 105 (5.5%) having VF. Low BMD values were detected in 501 patients (26.5%; 31.0% of females, 18.6% of males).

Conclusions

We observed high diagnostic accuracy of opportunistic osteoporosis screening using AI algorithms for detecting VF and low BMD. AI-based opportunistic screening of osteoporosis and VF in chest CT scans can facilitate the identification of high-risk cohorts.

Introduction

Osteoporosis is a significant health concern worldwide, particularly among the aging population. It is characterized by low bone mineral density (BMD) and deteriorated bone microarchitecture, leading to an increased susceptibility to fractures [1]. Postmenopausal women and men aged over 50 years are at a high risk of osteoporosis [2]. The prevalence of osteoporosis is expected to rise due to increasing life expectancy and the aging population.
Dual-energy X-ray absorptiometry (DXA) is widely used for assessing BMD and diagnosing osteoporosis based on T-scores, as recommended by the World Health Organization [1]. However, some studies have suggested that routine DXA screening for at-risk individuals may not be economically feasible [2]. Vertebral fractures (VF) are another indicator of osteoporosis, detectable through various imaging modalities [3]. VFs are typically underreported [4] due to patients not exhibiting specific symptoms and radiologists overlooking vertebral abnormalities on computed tomography (CT) scans [5]. Some studies suggest an opportunistic screening approach for osteoporosis, leveraging CT scans performed for other clinical indications [6].
Opportunistic CT screening for osteoporosis utilizes various approaches. These include qualitative models for VF detection [7], morphometric models for vertebral height measurement [8], and prognostic models for determining repeated fractures [9]. Artificial intelligence (AI) algorithms are also employed for determining regions of interest (ROI) inside the trabecular bone and assessing BMD or Hounsfield units (HU) [10]. Additionally, indirect BMD assessment using HU values [6,11], fully automated bone mineral densitometry following an asynchronous calibration [12], and automated BMD assessment with texture analysis [13] are used. A recent review analyzed different AI solutions for osteoporosis, focusing on VF detection and osteoporosis screening [14].
In individuals at risk (men and women over 50 years old), a decline in BMD is more frequently observed than VF. While VF occur in only 7% of osteoporotic cases [15], low BMD is found in 28.99% of women and 13.53% of men [16]. Therefore, opportunistic screening for osteoporosis using chest CT data, combined with the application of AI for VF detection [6,8,17] and ROI selection for BMD measurement [16], may maximize the effectiveness.
A previous paper proposed a morphometric algorithm for VF detection using convolutional neural networks (CNN), allowing quantification of vertebral morphometry [8]. This algorithm was updated to allow for the selection of the ROIs within the vertebrae and measurement of HU values, which are correlated with BMD [18]. As part of the project “Experiment on the use of innovative computer vision technologies for medical image analysis and subsequent applicability in the healthcare system of Moscow” (Experiment), this algorithm processed 59,482 CT chest studies within the Moscow Unified Radiological Information System (URIS) system over a period of 7 months (01.10.2021–29.04.2022).
This study aimed to confirm and evaluate the performance of opportunistic osteoporosis screening using AI in chest CT scans. The AI algorithm assessed both VF and low trabecular BMD. The objective was to determine the efficiency of this AI-enabled opportunistic screening approach, which combines VF detection and BMD measurement.

Materials and Methods

Ethics statement

This study was approved by the Independent Ethics Committee of the Moscow Regional Office of the Russian Society of Radiologists and Radiographers on February 18, 2021 (approval no., 2/2021).

Study design

Retrospective cohort study.

Patient profiles

This retrospective AI-based study analyzed routine chest CT scans performed during the peak of the coronavirus disease 2019 (COVID-19) pandemic across seven medical facilities (four inpatient and three outpatient) over a 1-month period (June 9, 2021 to June 30, 2021). This study is part of a larger initiative, a unique prospective multi-center study exploring the use of clinical decision support systems leveraging data analyzed using advanced technologies. This initiative has analyzed 13.4 million CT studies using 54 AI algorithms from various companies from 2020 to 2024. The AI algorithm used in the present study has been participating in this “Experiment” since 2021 focusing on detecting compression fractures of vertebral bodies (osteoporosis).
The inclusion criteria were patients over the age of 50 years who underwent a standard chest CT scan (scan parameters: tube voltage, 120 kVp; slice thickness, 1.0 mm; tube current selected automatically using Sure Exposure three-dimension [3D]; target noise standard deviation: 10 HU). Images were reconstructed using FC08 and FC51 kernels for soft tissue and lungs, respectively. The scans were performed on seven Aquillion 64 CT scanners (Canon Medical Systems, Otawara, Japan).
The exclusion criteria were processing errors; data transmission errors; CT images with significantly degraded quality caused by artifacts (including ring artifacts); reconstructed slice thickness over 3 mm; only lung kernel reconstruction; VF outside of the scan area; or congenital spine deformity.

Description of the AI algorithm

The morphometric CNN-based AI algorithm, named Genant-IRA, was developed by a Russian company IRA Labs Inc. in 2021. It is an extended version of the algorithm developed earlier [8,17]. The algorithm operates in two stages. In the first stage of the image processing pipeline, the algorithm identifies the center of each vertebra to create the central sagittal plane. It identifies the spinal column in 3D images using an approach based on soft-argmax. A reconstructed sagittal slice (1-cm thick), in the form of a curved reconstruction along the spinal column, is formed as a two-dimensional image. In the second stage, the algorithm performs morphometric analysis of vertebral bodies. Using the YOLOv3 architecture, it automatically detects vertebral bodies on the sagittal slice, identifies 6 points corresponding to the anterior, middle, and posterior vertebral body heights, and calculates the compression deformity index (expressed as a percentage) (Fig. 1). The compression deformity index is calculated for each vertebra using the following formula: Maximum height among three measurements (anterior, middle, and posterior height) minus the minimum height divided by the maximum height and multiplied by 100 to express the result as a percentage. More information is provided in Appendix 1.
The compression deformity is evaluated using the established H. Genant classification. Notably, several publications have observed that Genant grades 2–3, which correspond to vertebral compression deformities exceeding 25%, exhibit more concordant data [2,17]. In accordance with these recommendations, the AI algorithm assigns labels to the results as follows: (1) vertebral height loss of less than 25% (Genant 1) is labeled green (indicating no compression deformity, No Def); (2) a 25%–40% loss of height (Genant 2) is labeled yellow (indicating vertebral compression deformity, VCD); and (3) a loss of height >40% (Genant 3) is labeled red (indicating a VF).
Additionally, the AI algorithm delineates the ROI within the vertebrae and quantifies the corresponding HU values. These values are subsequently utilized to determine BMD through an asynchronous calibration procedure, as described in the Appendix 2. The FC08 kernel reconstruction was employed for HU measurement analysis. For each ventral surface from the 11th thoracic vertebra (T11) through the third lumbar vertebra (L3), excluding instances where a VCD (>25%) or VF is present, the AI algorithm sets a 1 cm trapezoid-shaped ROI on the reconstructed sagittal section (Fig. 1A). To ensure accurate measurements, the ROI is positioned in the anterior region of the vertebra, avoiding the basal-vertebral vein. The ROI edges are placed 3 mm away from the upper and lower endplates, as well as the cortical layer (Fig. 1A).
When the algorithm detects a mean trabecular attenuation of less than 150 HU within the ROI, the measurement result is displayed in a box situated to the right of the vertebra (Fig. 1). The box is color-coded to facilitate quick interpretation: orange indicates low values (<100 HU), while yellow denotes medium values (<150 HU) (Fig. 1). The threshold values of 100 HU and 150 HU were selected based on the findings of Alacreu et al. [11] and Graffy et al. [19].
The AI algorithm demonstrated satisfactory performance in detecting VF when tested on real-world data, with a sensitivity of 0.982 (95% confidence interval [CI], 0.960–1.00), specificity of 0.869 (95% CI, 0.855–0.882), and accuracy of 0.874 (95% CI, 0.859–0.889). The threshold for AI pathology detection was set at a compression deformity index of 25%.
The AI algorithm output examples are illustrated in Fig. 1, showing CT images of patients with VF (Fig. 1A), VCD (Fig. 1B), and No Def (Fig. 1C). All the CT images in Fig. 1 exhibit reduced BMD corresponding to osteoporosis (<80 mg/mL) according to the American College of Radiology (ACR) criteria. These BMD values were obtained using asynchronous quantitative computed tomography (QCT) [20].
The AI algorithm was connected to the picture archiving and communication system as part of the URIS. The URIS is built on the Agfa IMPAX Agility platform (Agfa Healthcare N.V., Mortsel, Belgium), which provides access to all radiological devices in the medical facilities subordinate to the Moscow Health Care Department. The data processed by the AI algorithm were made available in the URIS as DICOM Secondary Reporting images and Secondary Capture images. All CT images were fully anonymized before being transmitted to the AI algorithm.

Asynchronous quantitative computed tomography

Asynchronous QCT is a method that enables the quantification of BMD without the need for a calibration phantom during CT scanning [21]. According to the International Society for Clinical Densitometry (ISCD) 2023 guidelines [22], asynchronous QCT can be applied provided that HU boundaries have been validated and the stability of the CT scanner has been proven. This can be achieved through CT scanner calibration using phantoms, a process that is also employed in asynchronous QCT [21].
For the purpose of this study, asynchronous QCT calibration was employed to convert HU values to BMD values (mg/mL) and to verify the stability of the CT scanners. At the outset of the study, all CT units underwent calibration. This calibration process was performed using the PHantom Kalium (PHK) phantom which features four different mineral concentration samples [23]. As a result of this procedure, the stability of the CT scanner was confirmed and a calibration line for converting HU values to BMD values was established. The asynchronous QCT calibration enables the application of the ACR criteria for diagnosing osteoporosis (BMD <80 mg/mL) and osteopenia (80 mg/mL< BMD <120 mg/mL) following the conversion of HU values within the trabecular bone of vertebrae to BMD values [20]. However, the ISCD 2023 guidelines recommend utilizing spinal trabecular BMD measured by QCT as a predictor of VF [22].
The results of QCT calibration revealed that CT attenuation values of 105.6 HU (min 104.6 HU; max 107 HU) corresponded to a BMD of 80 mg/mL. The narrow confidence interval suggests that detecting osteoporosis without asynchronous calibration may be feasible, provided that the scanner operation remains stable, as emphasized in the ISCD 2023 guidelines. A detailed description of the PHK phantom and the calibration procedure are presented in Appendix 2.

Analysis and statistical processing

The AI processing results were made available as spreadsheet data for all patients, accompanied by attached sagittal CT images in DICOM Secondary Capture format. Each CT image and AI algorithm outcome was independently reviewed by three radiologists with 1, 2, and 5 years of experience, respectively. Each radiologist assessed the presence or absence of VF and conducted a morphometric assessment in the URIS by labeling the vertical dimensions of the vertebral bodies (anterior, middle, and posterior) to differentiate No Def, VCDs, and VFs. A deformation index threshold of 25% was established to differentiate between VF and VCD states. In addition, the experts assessed changes that are characteristic of VF, including endplate involvement. Subsequently, all data were verified by two experts with 15 and 35 years of experience in radiology. The verification was carried out via expert opinions and involved confirmation of all identified VFs. All radiologists and experts adhered to a published guideline [24]. Notably, prior assessments have revealed minimal variability among radiologists when performing markup tasks, with differences of approximately 0.1%.
To assess the performance of opportunistic osteoporosis screening, we compared groups of patients with VF, VCD, and No Def. We also estimated the number of patients with low average BMD (<80 mg/mL) and those with normal BMD. Additionally, we analyzed the distribution of VF and VCD across different vertebral numbers and evaluated the corresponding BMD characteristics for other vertebrae. The relationship between the compression deformity index and average BMD was also investigated.

Results

Study population

Between June 9, 2021 and June 30, 2021, the AI algorithm analyzed 3,308 chest CT studies. Patients aged 20–50 years were excluded from the evaluation of the algorithm’s performance based on the opportunistic screening outcomes. The study design is illustrated in Fig. 2. Of the total patients, 1,918 (58%) were aged above 50 years. We excluded 27 cases (1.4%) due to the following reasons: data transmission errors (17 patients, 0.8%); motion artifacts (four patients, 0.2%); and processing errors (six patients, 0.3%). Additionally, three patients (0.1%) were excluded due to spinal dysplasia, a T9 vertebral body deformity unrelated to a compression fracture, and a congenital deformity of T7–T8 with a perineural cyst. Two patients had VF below the AI-labeled area. Thus, 1,888 subjects (mean age: 66.3±8 years; male-to-female ratio: 0.63) were included in the final analysis.

Opportunistic screening for osteoporosis in chest CT during COVID-19 pandemic using the AI algorithm

The distribution of patients with VF, VCD, and those without deformations (No Def) is presented in Table 1. VF were identified by the AI algorithm and verified by an experienced radiologist. VCDs were detected by the AI algorithm as cases with a measured deformation index exceeding 25%. Patients with a deformation index of less than 25% were categorized as No Def. In addition to these characteristics, the distribution of low average BMD (<80 mg/mL) was estimated for all patient groups.
VCD (>25%) was detected by the AI algorithm in 336 patients (17.8%), of which 105 patients (5.5%) had VF. In 231 patients (12.2%), VCD was observed without qualitative signs of VF. Thus, the prevalence of VF in those aged over 50 years with VCD >25% was 31.2% (105/336 patients).
Most patients with VF had low BMD while patients in VCD and No Def groups were more likely to have BMD >80 mg/mL. Notably, 79 patients (4.2%) with VFs had osteoporotic BMD. However, a significant proportion of patients without VF also had low BMD values: 38.5% (89/231) of patients with some features of VCD and 21.5% (334/1,552) in the No Def group. Overall, 501 patients (26.5%) had low BMD values, while CT images of only 105 patients (5.5%) indicated VF.
The BMD results from the AI algorithm were unavailable for 15 subjects due to limited scanning length, which did not cover the spine below the T11 vertebral level.
The largest number of VF were found in patients aged 80–90 years, with 40 patients (16.8% of the total number of patients in this age group), and in patients aged 70–80 years, with 30 patients (7.7%). For patients aged 60 to 70 years, this value was 16 (2.7%), while only 11 patients under 60 years (1.9%) had VF. The smallest number was noted for the group older than 90 years, with eight patients (29.6%).
Fig. 3 illustrates the distribution of VF (a) and VCD (b) across different vertebrae levels, ranging from C5 to L4. The fraction values were calculated by dividing the number of patients with VF or VCD at a specific vertebra level by the total amount of patients in the VF (NVF=105) and VCD (NVCD=231) groups. The bar charts display the distribution of minimum BMD values for each vertebra with VF (a) or maximum VCD (b) in T11–L4 vertebrae among two groups: those with BMD values <80 mg/mL and those with BMD values between 80 and 120 mg/mL. As evident from Fig. 3A, the majority of VF cases occurred at the lower thoracic spine (T11 and T12) and the first vertebra of the lumbar spine (L1). Vertebrae L2–L4 were not always included in the scan length. The distribution of vertebrae in the studies was as follows: T11 (1,854 [98.1%]), T12 (1,681 [89.0%]), L1 (1,112 [59.9%]), L2 (427 [22.6%]), L3 (70 [3.7%]), L4 (6 [0.3%]), and L5 (1 [0.1%]). Among patients with VF, the fraction of cases with minimum BMD values below 80 mg/mL was larger than those with BMD values between 80 and 120 mg/mL. Fig. 3B presents the distribution of cases with the maximum VCD among vertebrae. For this group, the maximum VCD was observed in vertebrae T7, T8, and T11. Among all vertebrae with the maximum VCD, the minimum BMD values were either lower than 80 mg/mL or between 80 and 120 mg/mL. However, 447 patients had normal minimum BMD values (>120 mg/mL). Notably, some patients in the VF and VCD groups also had lower minimum BMD values.

Discussion

In this study, opportunistic screening of osteoporosis using the AI algorithm for VF detection and BMD quantification showed satisfactory performance. The overall prevalence of VF, as detected by the AI algorithm, was 5.5% (4.9% in men and 5.9% in women) (Table 1). Our findings are consistent with the incidence of VF reported in a previous study using abdominal CT scans for opportunistic screening in a different patient sample, where VFs were detected in 6.3% of patients from both genders [12]. In our study, the prevalence of VCD and VF in patients aged ≥50 years was 17.8% (Table 1). These findings are consistent with data from a European study spanning 19 countries [25], which reported an average VCD prevalence of 12% in both men and women aged 50–79 years using the morphometric method of McCloskey et al. [26] and Eastell et al. [27]. In previous Russian studies, VF was detected in 6.6%–6.9% of women and in 6.4%–10.2% of men aged over 50 years [28]. Additionally, Lesnyak et al. [15] reported VF detection rates of 7% in women and 7.2% in men [15]. The slightly lower relative number of detected VF in our study is probably related to the analysis being limited to the thoracic spine and the first lumbar vertebrae. The Th11 vertebra was included in the CT scanning length for 96% of cases but the L3 level was included in only 4%. The distribution of VF among vertebrae corresponds with data acquired by Fujiwara et al. [29], who reported the prevalence of VF cases for T11–T12 and L1 vertebrae. De Smet et al. [30] found a similar distribution of VCD among vertebrae, with the highest fractions for T7–T8 and T11–T12. Minor discrepancies have been observed in the accuracy metrics of the AI algorithm for detecting vertebrae in the thoracic and lumbar spine. The sensitivity was 0.95 (95% CI, 0.947–0.953) for the thoracic spine and 0.91 (95% CI, 0.905–0.916) for the lumbar spine. The specificity was 0.89 (95% CI, 0.887–0.895) for the thoracic spine and 0.94 (95% CI, 0.933–0.939) for the lumbar spine [31].
The importance of VF diagnosis and the differential diagnosis of VCD are highlighted in related work [24,28]. Osteoporosis diagnosis poses a challenge due to its asymptomatic nature, resulting in a large pool of patients with evidence of osteoporosis going undetected during routine CT studies. To address this, various approaches have been developed to perform opportunistic screening for VF and reduced BMD using existing CT data from other clinical indications [17,32,33], including CT coronary angiography for the T6–T9 thoracic spine [34]. The validity of this approach could be explained by comparing the potential number of VF in patients over 50 years old with cases of decreased BMD. While incidents of VF were observed in 7% of cases [15], a decrease in BMD to the level of osteoporosis was recorded in 28.99% of women and 13.53% of men [16]. Notably, our study identified 23 patients (1.2%) with VF and BMD >80 mg/mL, highlighting the importance of BMD measurement in avoiding misdiagnosis. Therefore, analyzing both VF and reduced BMD in chest CT imaging enhances the efficiency of opportunistic screening.
It is also possible to determine a decrease in BMD from HU data without CT scanner calibration. Alacreu et al. [11] showed that the criterion for diagnosing osteoporosis could be an L1 vertebra density <73 HU (90% probability), while “suspected osteoporosis” corresponded to 74< HU <116 and “norm” to >160 HU. Graffy et al. [19] substantiated the possibility of opportunistic osteoporosis screening using only HU values. Another study noted that densities below 100 HU indicate severe osteoporosis, with a VF probability of up to 31.9%. Others have suggested an L1 vertebra HU value of 110 as the threshold level for osteoporosis, with >90% specificity [35].
This study was performed during the COVID-19 pandemic using chest CT scans performed for various clinical indications worldwide. While radiologists primarily focus on lung pathology, leveraging opportunistic data on VF and BMD has enabled the detection of relevant, yet often unsuspected pathology [36]. In 2020, approximately 439,000 chest CT studies were performed in Moscow during the COVID-19 pandemic in patients aged over 50, corresponding to 7% of this age group. Considering the incidence of osteoporosis across the age groups of interest (7% with VF) [15], osteoporotic BMD in 13% of men and 29% of women [22], the introduction of AI-powered opportunistic screening for osteoporosis is expected to yield 21,000 patients with VF and 68,000 patients diagnosed with osteoporotic BMD annually. Moreover, radiologists accurately detect and report VF on CT images in only a minority of cases [4], although increasing awareness may lead to improvements in this area. Our data reveal that radiologists correctly interpreted VF during routine CT image readings in only 20 out of 105 patients (19.0%). These data underscore the importance of incorporating opportunistic screening capabilities into routine clinical practice.
In the future, the AI algorithm can serve as a double-reading tool for radiologists, similar to its suggested application in mammography [37]. After uploading a CT study into URIS, the AI algorithm automatically processes the CT images to detect any vertebral VCD and VF, while also estimating BMD values, generating a report in the DICOM Structured Reporting format. By leveraging the AI algorithm, radiologists can identify vertebrae with suspected VCD or reduced BMD, thereby minimizing false-negative results.
It is important to note that most qualitative AI algorithms only detect the presence of VF by indicating the probability of pathology, without specifying the compression deformity index. VF typically alters the vertebral shape, but not all deformities are caused by fractures [25]. Recent studies, such as Wang et al. [38], have demonstrated the potential of AI algorithms in diagnosing various types of vertebral diseases, including osteoporotic VF, old fractures, Schmorl’s node, Kummell’s disease, and previous surgeries. Although the results are promising, the algorithm struggled with accurately identifying Schmorl’s node [38]. In this context, morphometric AI algorithms offer greater accuracy and promise for opportunistic osteoporotic VF diagnosis. However, these models may lead to false-positive VF diagnoses and require further development, including improved identification of VF signs or incorporation of additional data (BMD, gender, age, and others) to enhance specificity.
Opportunistic screening of osteoporosis by chest CT has certain limitations. The most significant one is that chest CT scans do not include most of the vertebrae with the greatest mechanical load, specifically the lumbar spine. Only 59.1% of studies include the L1 and L2 vertebrae, which are recommended by the ISCD 2023 position for measuring BMD by 3D CT scans [19]. Additionally, not all studies can be correctly processed by AI algorithms for automatic BMD determination. Some scans may be performed on non-calibrated scanners or asynchronous scanners, which can affect the accuracy of BMD measurements. Furthermore, according to the ISCD 2023 position, an HU value of ≤100 is considered indicative of osteoporosis; however, using this threshold may reduce the accuracy of the methods [19]. Another limitation is the potential distortion of HU estimates when using the “sharp” kernel for visualization of the lung parenchyma. Additionally, HU values may be inaccurate when using low-dose or ultra-low-dose CT technologies. Moreover, the patient population referred for chest CT scans may differ from the general population, as they often have suspected chest pathology or undergo repeat studies. Therefore, opportunistic osteoporosis screening based on chest CT may not provide full population coverage for detecting osteoporosis. More effective approaches, such as the Fracture Risk Assessment Tool (FRAX) assessment followed by DXA, may be necessary for comprehensive osteoporosis screening. However, special epidemiological conditions, such as the COVID-19 pandemic, can significantly increase the number of chest CT scans performed, thereby enhancing the detection of osteoporosis when opportunistic patient screening methodologies are in place.
This study has several limitations. The data on the prevalence of VCD/VF are a byproduct of AI validation and, although performed opportunistically, only indirectly reflect real-world values. To quantify the population prevalence of these conditions more accurately, further investigations considering age group sizes and lumbar spine CT studies are necessary. Additionally, the L1 and L2 vertebrae, typically included in BMD assessments, were only present in a small percentage of chest CT scans. Therefore, T11 vertebrae were used as a more reliable alternative to determine BMD.

Conclusions

Our study demonstrates the efficiency of opportunistic osteoporosis screening using chest CT scans performed for diagnosing COVID-19-associated pneumonia, in conjunction with a morphometric AI algorithm. This approach enabled the detection of VF and reduced BMD in patients over 50 years of age. Opportunistic screening facilitates the identification of high-risk patients who require further evaluation to confirm the diagnosis. The AI algorithm can serve as a valuable second-reader tool, enhancing osteoporosis diagnostics by detecting both VF and reduced BMD.

Key Points

  • Osteoporosis is characterized by low bone mineral density (BMD) and impaired bone microarchitecture, leading to increased fracture risk. Postmenopausal women and men aged over 50 years have a high risk of hip fracture.

  • The World Health Organization recommends dual-energy X-ray absorptiometry (DXA) to determine BMD and diagnose osteoporosis. Wide-spread DXA screening may not be economically feasible. Opportunistic screening using computed tomography imaging and artificial intelligence (AI) algorithms can facilitate osteoporosis diagnosis.

  • An AI algorithm was developed to automatically detect vertebral fractures (VFs) and measure BMD. During the coronavirus disease 2019 pandemic, this algorithm demonstrated high sensitivity and specificity for identifying VFs and assessing BMD.

Notes

Conflict of Interest

The authors, affiliated with “IRA Labs Inc., Moscow, Russia” are the developers of the Genant-IRA software product used in the work. Except for that, no potential conflict of interest relevant to this article was reported.

Funding

This paper was prepared with the partial support of a group of authors, affiliated to “Research and Practical Clinical Center for Diagnostics and Telemedicine Technologies of the Moscow Health Care Department, Moscow”, as a part of the research and development effort titled “Development of a hardware and software suite for opportunistic screening of osteoporosis” (USIS No.: 123031400007-7) in accordance with the Order No. 1196 dated December 21, 2022 “On approval of state assignments funded by means of allocations from the budget of the city of Moscow to the state budgetary (autonomous) institutions subordinate to the Moscow Health Care Department, for 2023 and the planned period of 2024 and 2025” issued by the Moscow Health Care Department.

Author Contributions

Conceptualization: AVV. Methodology: AVP, PJP, MGB, ZEB. Data curation: AVP, NDK, LRA. Statistical analysis: AAZ, TMB, ESA. Data anonymization: DSS. Investigation: ZRA. Software: MGB, MEP, ANB, AAZ. Validation: AVP, LAN. Supervision: YAV. Writing–original draft: AVP, ESA, ZRA. Writing–review & editing: PJP, MGB, ZEB, IAB. Final approval of the manuscript: all authors.

Fig. 1
The examples of artificial intelligence algorithm outcome. (A) A patient with vertebral fracture (VF), bone mineral density (BMD) <100 Hounsfield units (HU). (B) A patient with vertebral compression deformities (VCD) and <100 HU. (C) A patient without any vertebral deformities, but <100 HU.
asj-2024-0314f1.jpg
Fig. 2
Study design. CT, computed tomography; VCD, vertebral compression deformities; BMD, bone mineral density; VF, vertebral fracture.
asj-2024-0314f2.jpg
Fig. 3
The fraction of vertebrae fracture (VF) (A) and vertebral compression deformities (VCD) (B) for each vertebra from C5 to L4 calculated as number of patients with VF or VCD for the certain vertebra divided by the total amount of patients with VF (NVF=105) and VCD (NVCD=231). For each vertebra with VF (A) or maximum deformation (B), the distribution of minimum bone mineral density (BMD) of other vertebras (T11–L5) among three groups (<80 mg/mL, 80–120 mg/mL, >120 mg/mL) are presented as bar charts with corresponding fractions.
asj-2024-0314f3.jpg
Table 1
Opportunistic screening for osteoporosis in 1888 patients during the COVID-19 pandemic
Pathology Total Female Male
Total 1,888 (100.0) 1,155 (61.2) 733 (38.8)
VCD and VF 336 (17.8) 174 (15.1) 162 (22.1)
 VF 105a) (5.5) 69 (5.9) 36 (4.9)
  VF+ (BMD <80 mg/mL) 79 (4.2) 62 (5.4) 17 (2.3)
  VF+ (BMD >80 mg/mL) 23 (1.2) 4 (0.3) 19 (2.6)
 VCD 231 (12.2) 105 (9.1) 126 (17.2)
  VCD+ (BMD <80 mg/mL) 89 (4.7) 52 (4.5) 37 (5.0)
  VCD+ (BMD >80 mg/mL) 142 (7.5) 53 (4.6) 89 (12.1)
No Def 1,552b) (82.2) 981 (84.9) 571 (77.9)
 No Def (BMD <80 mg/mL) 334 (17.2) 249 (21.5) 85 (11.5)
 No Def (BMD >80 mg/mL) 1,206 (63.9) 725 (62.8) 481 (65.6)
BMD <80 mg/mL 501 (26.5) 358 (31.0) 136 (18.6)

Values are presented as number of patients (%).

VCD, vertebral compression deformities (deformation index >25% as measured by artificial intelligence); VF, vertebral fractures (verified by experts); BMD, mean bone mineral density; No Def, no deformities (deformation index <25%).

a) 3 patients don’t have BMD measurements because of technical issues (female: n=3).

b) 12 patients don’t have BMD measurements because of technical issues (female: n=7, male: n=5).

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Appendices

Appendix 1

Detailed description of the artificial intelligence model

The morphometric convolutional neural networks-based artificial intelligence (AI) algorithm (named Genant-IRA) was developed IRA Labs Inc. in 2021. Several studies have been published to support the development of this product [A1–A4].
The algorithm is designed to detect vertebral fractures (VFs), quantify fracture severity, and measure bone mineral density (BMD) within non-fractured vertebrae. The Genant-IRA algorithm operates through a three-stage pipeline.

1. Spine localization and straightening

The description of this stage is provided in a published paper [A3]. This stage utilizes a three-dimensional (3D) UNet-like fully convolutional neural network to predict the probability of each voxel being situated near the vertebral column. The network’s output is then processed in two ways [A3] (Fig. A1): (1) A two-dimensional soft-argmax operation is applied along the xOy axes to obtain the spine coordinates in axial planes. (2) A global max-pooling operation is applied along the same axes to determine the probability of containing the spine at a given z coordinate.
Using the predictions from the first network, a 3D curve passing through the vertebral column is obtained, along with the limits within which it is defined. The image is then cropped accordingly and interpolated onto a new 3D grid, where the obtained curve becomes a straight vertical line.

2. Vertebrae detection and fracture quantification

The second stage of the Genant-IRA algorithm involves vertebrae detection and fracture quantification, as described in a previous paper [A3]. To perform vertebrae detection, the authors employed anchor-based translation-invariant encoding. This approach treats each pixel as an anchor relative to which the coordinates of 6 points are calculated. Finally, the authors used the same loss function as in [A1] to train the second network:
L=BCE(o^,o)+1I[oi=0]i=lNI[oi>0]Gi*MAE(eι^,el)
Where BCE (binary cross-entropy) is the log-loss between the real (o) and predicted (ô) objectness, MAE is the mean absolute error between real (ei) and predicted (êi) encoded keypoints’ coordinates for the ith vertebra, and Gi is the respective Genant score used for loss reweighting. Such a reweighting of regression loss was found very effective in balancing the network’s performance across vertebrae with different fracture severities.
Fig. A1
The spine localization pipeline [A3]. (A) Three axial slices from different body regions; head, thorax, legs. (B) The slices’ spatial position relative to the spine. (C) The predicted probability maps for each slice, the color intensity denotes the probability magnitude. (D) The final curve passing through the vertebral column (green), as well as the redundant parts (red) delimited by the spine limits (black, dashed).
asj-2024-0314f4.jpg

3. Bone mineral density measurement

The final stage of the Genant-IRA algorithm involves BMD measurement, as described in a previous paper [A4]. The AI algorithm defines the regions of interest (ROI) within the vertebrae and quantifies the corresponding computed tomography (CT) values. These CT values are used to determine BMD via an asynchronous calibration. For each ventral surface from the 11th thoracic vertebra (T11) through the third lumbar vertebra (L3), the AI algorithm sets a 1-cm thick trapezoid-shaped ROI on the reconstructed sagittal section. To avoid uncertainties in calculations, vertebrae with a VCD (>25%) or VF were excluded from these measurements. The ROI edges are positioned 3 mm from the upper and lower endplates and the cortical layer. The threshold levels for BMD measurement were established based on the previous studies by Alacreu et al. [A5] and Graffy et al. [A6]. Normal BMD values were considered for trabecular attenuation larger than 150 HU, medium values ranged from 100 to 150 HU, and low values were less than 100 HU.

4. Description of datasets

Datasets for training

  • 100 randomly selected images from the Moscow Radiology CTLungCa-500 dataset (LungCancer-500; https://mosmed.ai/en/data-sets/ct_lungcancer_500/) [A7].

  • A large private dataset that includes 402 chest and abdominal CT studies with annotated Genant segments using the same protocol as LungCancer500. The distribution of VFs was as follows: 667 mild deformations, 364 moderate deformations, 153 severe deformations, and 4,364 normal vertebrae. The annotation was performed by three experienced radiologists with at least 10 years of experience.

  • 191 additional chest, abdominal, and brain CT studies with annotated limits to improve the spine localization network performance.

Datasets for testing

  • The VerSe-2020 dataset consisting of over 300 multidetector CT images of various regions of the spine [A8].

  • Mosmed.ai test dataset: The dataset was prepared to test various algorithms using the principles described by Pavlov et al. [A9]. It consists of 50 studies with VFs and 50 age-matched healthy studies (Genant score ≥0.75). Cases were prepared carefully to test the algorithms under various conditions, such as vertebral ankylosis, vertebroplasty, and osteoblastic metastases. Only patient-level metrics are available for this dataset. The data is hidden from the developers; the test was conducted in real-time with 60 seconds response time requirement.

Performance metrics

Table A1
Spinal line localization metrics for Lung-Cancer-500 and VerSe-2020 datasets
Test Train Mean points 12 (mm) Limits MAE (mm)
Cancer500 Cancer500 0.92 (0.07) 0.03 (0.04)
Private 0.74 (0.06) 0.07 (0.08)
VerSe val VerSe 1.81 (0.20) 19.23 (3.42)
Private 1.30 (0.15) 18.37 (3.82)
VerSe test VerSe 1.72 (0.17) 18.76 (2.59)
Private 1.19 (0.16) 18.07 (3.10)

Cancer500 and VerSe: name of datasets.

MAE, mean absolute error; Val, validation data; test, test data.

Table A2
Vertebrae detection and severity classification metrics >25%
Test Train Vertebra detection Severity classification


Precision Recall ROC AUC Sens at Spec=0.9
Cancer500 Anchor-Boxes 0.994 (0.001) 0.953 (0.001) 0.955 (0.004) 0.863 (0.030)

Ours 0.991 (0.002) 0.990 (0.002) 0.959 (0.002) 0.885 (0.002)

Experts 0.999 (0.001) 0.994 (0.001) 0.971 (0.005) 0.936 (0.018)

Ours-private 0.993 0.991 0.981 0.950

VerSe Ours 0.947 0.886 0.951 0.848

Ours-experts 0.935 0.951 - -

Ours-private 0.896 0.973 0.970 0.908

Anchor-Boxes: the approach from our previous work [A1]. Both spine localization and vertebra analysis networks were trained on Lung-Cancer-500. Experts: ground truth; Ours: the proposed anchor-free approach, both networks were trained on Lung-Cancer-500. Ours-Private: the proposed approach, both networks were trained on the private dataset.

ROC, receiver operating characteristic; AUC, the area under the ROC curve; Sens at Spec, sensitivity at specificity.

Table A3
Binary classification metrics on VerSe for various grades of fractures: at least mild (G≤0.8) and at least moderate (G≤0.74)
Task Model Vertebra-level Patient-level


ROC AUC Sens at Spec=0.9 ROC AUC Sens at Spec=0.9
G0 vs. G1, G2, G3 Public 0.877 0.713 0.882 0.703

Private 0.906 0.777 0.911 0.807

G0 vs. G2, G3 Public 0.963 0.889 0.953 0.856

Private 0.979 0.952 0.962 0.919

G0, G1 vs. G2, G3 Public 0.951 0.848 0.936 0.806

Private 0.970 0.908 0.960 0.910

mosmed.ai Private NA NA 0.99 1.0

Values are presented as mean.

ROC, receiver operating characteristic; AUC, the area under the ROC curve; Sens at Spec, sensitivity at specificity; NA, not applicable.

Performance metrics of the algorithm are presented in the paper by Zakharov et al. [A3]. Performance metrics were obtained using 5-fold cross-validation (Tables A1A3).
Overall, the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to estimate the effectiveness of the AI algorithm in classifying VF severity (moderate and severe). These metrics were calculated using the publicly available dataset LungCancer-500. The AUC was 0.959±0.002, the sensitivity was 0.885±0.002, and the specificity was 0.900.

Appendix References

A1. Pisov M, Kondratenko V, Zakharov A, et al. Keypoints localization for joint vertebra detection and fracture severity quantification. Proceedings of the 23rd International Conference on Medical Image Computing and Computer Assisted Intervention–MICCAI 2020; October 4-8, 2020;Lima, Peru. Cham: Springer International Publishing; 2020. p. 723-32.
A2. Petraikin AV, Belaya ZE, Kiseleva AN. Artificial intelligence for diagnosis of vertebral compression fractures using a morphometric analysis model, based on convolutional neural networks. Probl Endokrinol (Mosk) 2020;66:48-60.
A3. Zakharov A, Pisov M, Bukharaev A. Interpretable vertebral fracture quantification via anchor-free landmarks localization. Med Image Anal 2023;83:102646.
A4. Artyukova ZR, Kudryavtsev ND, Petraikin AV. Using an artificial intelligence algorithm to assess the bone mineral density of the vertebral bodies based on computed tomography data. Med Vis 2023;27:125-37.
A5. Alacreu E, Moratal D, Arana E. Opportunistic screening for osteoporosis by routine CT in Southern Europe. Osteoporos Int 2017;28:983-90.
A6. Graffy PM, Lee SJ, Ziemlewicz TJ, Pickhardt PJ. Prevalence of vertebral compression fractures on routine CT scans according to L1 trabecular attenuation: determining relevant thresholds for opportunistic osteoporosis screening. AJR Am J Roentgenol 2017;209:491-6.
A7. Morozov SP, Gombolevskiy VA, Elizarov AB. A simplified cluster model and a tool adapted for collaborative labeling of lung cancer CT scans. Comput Methods Programs Biomed 2021;206:106111.
A8. Loffler MT, Sekuboyina A, Jacob A. A vertebral segmentation dataset with fracture grading. Radiol Artif Intell 2020;2:e190138.
A9. Pavlov NA, Andreychenko AE, Vladzymyrskyy AV, Revazyan AA, Kirpichev YS, Morozov SP. Reference medical datasets (MosMedData) for independent external evaluation of algorithms based on artificial intelligence in diagnostics. Digit Diagn 2021;2:49-66.
Appendix 2

Description of the PHK phantom and calibration methodology

The PHantom Kalium (PHK) phantom is a cylindrical device designed to simulate the lower spine region. It has an internal diameter of 200 mm and a length of 230 mm, with a 5 mm thick polymethyl methacrylate wall. Using high-precision milling on ultra-high-molecular-weight polyethylene fiber, four vertebra models were produced, each consisting of a cylinder (vertebra body) and a parallelepiped (cortical layer) (Fig. A1). The vertebrae sections are filled with various concentrations of a dipotassium phosphate solution (К2HPO4) to simulate different bone mineral density (BMD) levels. Table A1 contains the set values of volumetric BMD and projected areal density (cylinder+cortical layer). The accuracy of the set BMD values for this phantom is comparable to that of ESP (European Spine Phantom) phantoms. The PHK phantom can be used both for dual-energy X-ray absorptiometry (DXA) measurement accuracy evaluation and quantitative computed tomography (CT) (Table A1). To simulate the fat layer, 40 mm thick circular paraffin patches were used to cover the phantom’s outer side completely. During DXA with the simulated fat layer, the fat percentage was 32.14%.
The calibration procedure with the PHK phantom is presented in Fig. A2. The process begins with a CT scan of the PHK phantom, performed using standard clinical settings (Fig. A2). The phantom should be positioned precisely at the center of the field of view. The CT images are then reconstructed using standard kernels. The next step involves analyzing the signal intensity inside the region of interest (ROI). ROIs are placed at the level of the PHK-phantom samples L1–L4 (Table A1) for both cylinder and cortical parts. The mean (M) values for each ROI are collected.
The scanning and measurement procedure should be repeated five times to evaluate the stability of the CT scanner. Subsequently, the mean and standard deviation are calculated for each CT unit. The mean standard deviation among all CT facilities was 2.08 mg/mL (range, 1.46–2.64 mg/mL). This level of variability is considered clinically insignificant, demonstrating the stability of CT scanners included in this study.
Fig. A1
PHK (PHantom Kalium) phantom design. (A) Vertebrae section made of a cylinder that simulates the vertebra body, and a parallelepiped imitating a cortical layer. (B) The “vertebrae” were placed inside a cylinder with a diameter of 200 mm filled with water.
asj-2024-0314f5.jpg
Fig. A2
Image of the PHK (PHantom Kalium) phantom. (A) Appearance of the phantom when scanning on computed tomography (CT). (B) CT images of the phantom in the axial and the sagittal projections.
asj-2024-0314f6.jpg
Table A1
The PHantom Kalium features
Sample Volumetric BMD (cylinder, mg/mL) Set volumetric BMD (cortical layer, mg/mL) Set projected BMD (g/cm2) Set T-score for Lunar DXA (SD)
L1 50.09 250.54 0.586 −5.08 (osteoporosis)
L2 100.19 350.76 0.886 −2.58 (osteoporosis)
L3 150.39 451.01 1.177 −0.16 (normal)
L4 200.47 551.21 1.475 2.33 (normal)

The “vertebra” (sample) area of 17.5 cm2 is defined by the area of a parallelogram pertaining to a denser cortical layer. According to the evaluation of the expanded uncertainty for the set values the error for the set volumetric BMD is ±0.21%; projected areal density: ±0.9%. The highest difference between the volumetric and set BMD values for both L1 sections is 0.26%.

BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; SD, standard deviation.

Fig. A3
Results of phantom scanning: the calibration line in two phantom configurations “with fat” and “without fat.” vBMD, volumetric bone mineral density; QCT, quantitative computed tomography; PHK, PHantom Kalium; HU, Hounsfield units.
asj-2024-0314f7.jpg
Based on the results of the 5-time phantom scan, calibration straight lines were constructed, and a correction factor was determined (Fig. A3). The slope and intercept coefficient of the calibration line calculated for the “with fat” phantom configuration were used for further calculations. This ratio was used to convert intravertebral Hounsfield units (HU) to patient BMD. The average calibration equation obtained was BMD (mg/mL)=0.77×HU−0.48.
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