Dual-Energy Computed Tomography Applications in Rheumatology

Dual-energy computed tomography (DECT) has emerged as a transformative tool in the past decade. Initially employed in gout within the field of rheumatology to distinguish and quantify monosodium urate crystals through its dual-material discrimination capability, DECT has since broadened its clinical applications. It now encompasses various rheumatic diseases, employing advanced techniques such as bone marrow edema assessment, iodine mapping, and collagen-specific imaging. This review article aims to examine the unique characteristics of DECT, discuss its strengths and limitations, illustrate its applications for accurately evaluating various rheumatic diseases in clinical practice, and propose future directions for DECT in rheumatology.

Key points

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Dual-energy computed tomography (CT) (DECT) demonstrates high diagnostic performance in diagnosing gout, extending its capabilities into assessing disease severity, treatment response, and prediction by providing quantitative data.
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Certain scenarios may lead to underestimating or overestimating gout severity when using DECT, requiring awareness and applying strategies for accurate evaluation.
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Dual-energy CT can diagnose various other rheumatologic diseases and assess treatment responses by employing bone marrow edema visualization, iodine mapping, and collagen mapping techniques.

Introduction

Rheumatic diseases are associated with significant disability, loss of productivity, and reduction in quality of life, resulting in substantial impacts on individuals and society, imposing both economic and social burdens. These conditions affect individuals personally and impose substantial economic and social burdens on society. Since their first mention by Hippocrates in the fourth century, rheumatic diseases have evolved significantly, now standing at the forefront of molecular medicine and novel targeted therapies. This evolution underscores the need for accurate evaluation and diagnosis, integrating cutting-edge imaging techniques. ^,

Traditional computed tomography (CT) imaging, despite its utility, faces limitations in evaluating soft tissue inflammation, even when intravenous contrast agents are used. This is primarily due to its inherent challenges in contrast resolution, rendering it less effective than MRI or ultrasonography. As a result, the use of CT in rheumatology, beyond assessing bony structural changes, was historically limited. However, dual-energy CT (DECT) has emerged as a transformative tool in the past decade. Initially utilized in gout to differentiate and quantify monosodium urate crystals through its dual-material discrimination capability, the clinical applications of DECT have since expanded. It now encompasses various rheumatic diseases, utilizing advanced techniques, including bone marrow edema assessment, iodine mapping, and collagen-specific imaging. This review article aims to review the unique characteristics of DECT, discuss its strengths and limitations, and illustrate applications of DECT for accurately evaluating various rheumatic diseases in clinical practice.

Technical review of dual-energy computed tomography

DECT is the process of acquiring two separate image volumes of a single material which correspond to its exposure to two different x-ray energy spectra. The appearance of the material in the resulting two image volumes provides clues to the nature of the material. Table 1 shows a typical DECT protocol using a dual source implementation where two independant x-ray tubes provide two different energy spectra. ^, ^,

Table 1

Dual-energy computed tomography procotol

kVp (Low/High) ^a	90/sn150
mAs (Low/High)	Hand 226/226	Foot 202/188
Collimation (mm)	128 × 0.6
Rotation Time (s)	1
Section Thickness (mm)	0.75
Increment (mm)	0.5
Pitch	0.5

a This protocol applies to a Force DS CT scanner, Siemens Healthcare

Depending on the implementation, there may be no dose penalty associated with dual energy scanning compared to conventional single energy scanning. ^, A previous study demonstrated that the Computed Tomography Dose Index (CTDIvol) was 12% lower when using DECT with energy settings of 80 and 140 kVp compared to single-source CT with 120 kVp, without compromising image quality.

In addition to dual source dual energy, other implementations include: (1) Rapid tube voltage switching DECT, where a single tube quickly alternates between high and low energy voltages. (2) Split-filter DECT, wherethe X-ray beam is divided using gold and tin filters into two beams with different energies. (3) Dual-spin DECT, where the patient undergoes two consecutive acquisitions with different tube voltages. ^, The interpretation of a DECT acquistion requires vendor specific post-processing tools. ^,

Dual-energy computed tomography and gout

Detecting Uric Acid

DECT has gained clinical applicability based on its effectiveness in detecting monosodium urate (MSU) crystals (uric acid), representing one of its pioneering uses in musculoskeletal imaging. While both appear bright in a single energy image, DECT can distinguish MSU from bone. Pixels with MSU crystals can be color-coded for easy and straightforward detection, thereby enhancing diagnostic accuracy ( Fig. 1 ). ^, Color maps can be generated through post-processing and presented in both 2-dimensional cross-sectional images and 3-dimensional volume-rendering images, integrated with CT images ( Fig. 2 ). This integration allows for the simultaneous display of the anatomic site, enhancing the visualization of relevant structures. In the reconstructed image, uric acid is shown in green, the cortex in purple, and the trabecular bone in pink. However, these colors may vary depending on the vendor and specific settings. ^,

While the accuracy of DECT-based gout diagnosis may vary on the disease stage, most reports consistently indicate high diagnostic performance. A meta-analysis of 8 studies found a pooled sensitivity of 93.7% and a pooled specificity of 84.7% for gout diagnosis using DECT. This performance led to the inclusion of DECT in the 2015 update of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for gout.

The high diagnostic accuracy of DECT in identifying gout enables prompt initiation of gout management. Conversely, ruling out gout facilitates timely treatment of underlying medical conditions that mimic gout. Differential diagnoses associated with high attenuation changes on CT include calcium pyrophosphate dihydrate (CPPD), calcific tendinosis, tumoral calcinosis, and osteochondromatosis, each requiring distinct management approaches ( Fig. 3 ).

One of the salient capabilities of DECT is its ability to detect MSU tophi, even in deep tissue locations, thereby providing a map of tophi at a glance (see Fig. 1 ; Fig. 4 ). This feature augments limitations in clinical tophi evaluation. Various methods have been applied to detect and characterize tophi, such as direct measurements with Vernier calipers, digital photography with imaging software, and ultrasound. However, these methods are only suitable for surface or superficial tophi. Clinically detected subcutaneous tophi may not adequately reflect the overall burden or complications because they represent only a portion of the problem and may not account for crystal burden and local inflammatory changes.

Disease Severity and Monitoring

The utility of DECT in gout extends beyond diagnosis. DECT allows for the assessment of disease burden and severity by enabling the quantification of the total volume of MSU crystal deposition (see Fig. 2 ). MSU crystal volume assessment using DECT is reliable and reproducible when using the same CT scanner and software examinations, providing more quantitatively objective data when compared to physical measurements.

Treatment Response and Monitoring

Quantitative data also enable the monitoring of treatment response. Urate-lowering therapy (ULT) is an important long-term approach to treating gout. By dissolving MSU crystals, ULT reduces uric acid levels in the body, leading to symptom relief, suppression of gout flares, regression of tophi, and protection against joint damage. Traditionally, the endpoint target for ULT has been serum uric acid levels, as advocated by The Outcome Measures in Rheumatology (OMERACT) gout working group, ACR, and EULAR. However, the “treat-to-target” paradigm has been recently questioned by the American College of Physicians. ^, DECT has been reported to effectively reflect the decrease in MSU crystal treatment response and is increasingly recognized as a valuable method for monitoring gout. ^, Nonetheless, there is a possibility of underestimation of the MSU crystal deposition in specific circumstances, and data may vary based on the acquisition technique and workstation settings. Therefore, it is essential to exercise caution and strive to acquire images on the same machine with consistent post-processing settings whenever possible.

Prediction and Monitoring

Gout is known to be often linked to other conditions, including hypertension, diabetes, dyslipidemia, kidney stones, chronic kidney disease, and cardiovascular disease. The volume of MSU crystal deposition measured by DECT has demonstrated the ability to predict gout flares, cardiovascular risk, diabetes mellitus, and mortality. ^, In a 12-month observational study, it was reported that for each additional 1 cm ³ of MSU crystals measured by DECT, the risk of experiencing a gout flare increased by a factor of 2.03. In another study with 128 gout patients, the measurement of MSU crystal volume using DECT emerged as a valuable biomarker for predicting the likelihood of developing new cardiometabolic complications and mortality.

Pathophysiology

Crystal deposition is a central pathogenic cause of gout associated with structural bone changes. However, the current clinical staging system for hyperuricemia is based on clinical features, which depend on individual responses to crystal deposition rather than a pathologic basis. Recent research studies using DECT contribute to an improved understanding of pathophysiology and highlight the importance of evaluating MSU crystal deposition. ^,

A significant number, about 15% to 33%, of individuals with asymptomatic hyperuricemia have been found to exhibit evidence of MSU crystal deposition, which is thought to indicate a preclinical stage. ^, This has recently led to a conceptual change in understanding the relationship between hyperuricemia and gout. ^, It is suggested that these silent MSU crystal deposition in asymptomatic hyperuricemia is linked to joint inflammation and cardiovascular disease. ^, Consequently, there is a growing interest in crystal deposition, leading to the proposal of new staging systems and management approaches for its evaluation. Similarly, using DECT to assess crystal deposition provides deeper insights into asymptomatic hyperuricemia.

What is Causing False Negatives?

Recently, there has been a growing consensus that DECT may lack sufficient sensitivity in the early stage of gout ( Fig. 5 ). This presents a significant challenge, especially since this initial stage is critical for distinguishing gout from other conditions and ensuring timely intervention to prevent the progression to advanced tophaceous gout. Studies have reported high sensitivity of DECT in detecting gout; however, most studies have focused on long-standing chronic or tophaceous gout. ^, A study indicated that DECT sensitivity varies depending on the duration of gout, with low sensitivity at 35.7% during the first onset, 61.5% for less than 2 years, and a higher sensitivity of 92.9% for patients with gout lasting over 2 years.

The discrepancy in voxel sizes between DECT and MSU crystals can explain this phenomenon. Crystallized uric acid particles typically measure approximately 1 to 20 μm, whereas the voxel size in DECT is around 600 μm. Consequently, DECT faces challenges in detecting small deposits of MSU crystals during the early stages. Another reason is that, unlike ultrasound, DECT only detects the crystal component of tophi, without revealing the soft tissue component composed of inflammatory and connective tissue. Additionally, the low density of crystals can make chemical decomposition difficult, as they may have smaller Hounsfield Unit (HU) differences at different energies. Hence, the following conditions will likely result in an underestimation of crystals: early-stage gout with small crystals, liquid crystals, crystals in fluid, low-density crystals, calcified crystals, and crystals under treatment. ^,

To avoid underestimating crystal deposition in DECT scans, reducing the minimum HU threshold to 120 or 130 can be beneficial ( Fig. 6 ). However, it is important to note that in certain machines and settings, this adjustment may significantly increase the likelihood of producing artifacts. An alternative approach is using ultrasound as a diagnostic tool (see Fig. 5 ). ^, ^, A recent meta-analysis comparing the diagnostic accuracy of DECT and ultrasound, encompassing 28 studies, showed that ultrasound exhibited a higher pooled sensitivity of 93% compared to DECT, which showed a sensitivity of 75%, especially in early disease stages (≤2 years). Ultrasound images of gout typically display the double contour sign, hyperechoic spots, tophi, and eccentric bony erosion. Unlike DECT, ultrasound can evaluate both the crystalline and soft tissue components and is easy to perform and cost-effective, making it particularly useful in aiding DECT, especially in the early stages of the disease ( Table 2 ).