Dual-energy computed-tomography-based discrimination between basic calcium phosphate and calcium pyrophosphate crystal deposition in vivo

Abstract

Background: Dual-energy computed tomography (DECT) is being considered as a non-invasive diagnostic and characterization tool in calcium crystal-associated arthropathies. Our objective was to assess the potential of DECT in distinguishing between basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystal deposition in and around joints in vivo. Methods: A total of 13 patients with calcific periarthritis and 11 patients with crystal-proven CPPD were recruited prospectively to undergo DECT scans. Samples harvested from BCP and CPP calcification types were analyzed using Raman spectroscopy and validated against synthetic crystals. Regions of interest were placed in BCP and CPP calcifications, and the following DECT attenuation parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (Rho), and effective atomic number ( Zeff). These DECT attenuation parameters were compared and validated against crystal calibration phantoms at two known equal concentrations. Receiver operating characteristic (ROC) curves were plotted to determine the highest accuracy thresholds for DEI and Zeff. Results: Raman spectroscopy enabled chemical fingerprinting of BCP and CPP crystals both in vitro and in vivo. DECT was able to distinguish between HA and CPP in crystal calibration phantoms at two known equal concentrations, most notably by DEI (200 mg/cm3: 0.037 ± 0 versus 0.034 ± 0, p = 0.008) and Zeff (200 mg /cm3: 9.4 ± 0 versus 9.3 ± 0, p = 0.01) analysis. Likewise, BCP calcifications had significantly higher DEI (0.041 ± 0.005 versus 0.034 ± 0.005, p = 0.008) and Zeff (9.5 ± 0.2 versus 9.3 ± 0.2, p = 0.03) than CPP crystal deposits with comparable CT numbers in patients. With an area under the ROC curve of 0.83 [best threshold value = 0.0 39, sensitivity = 90. 9% (81.8, 97. 7%), specificity = 64.6% (50.0, 64. 6%)], DEI was the best parameter in distinguishing between BCP and CPP crystal depositions. Conclusion: DECT can help distinguish between crystal-proven BCP and CPP calcification types in vivo and, thus, aid in the diagnosis of challenging clinical cases, and in the characterization of CPP and BCP crystal deposition occurring in osteoarthritis.

Can Dual‐Energy Computed Tomography Be Used to Identify Early Calcium Crystal Deposition in the Knees of Patients With Calcium Pyrophosphate Deposition?

“…In addition, our study emphasizes the main potential clinical utility of DECT in calcium crystal–associated rheumatic and musculoskeletal diseases: characterizing larger (“macro”)/higher‐concentration crystal aggregates, rather than lowering the detection limit for early (“micro”)/lower‐concentration calcium crystal deposition not visible with conventional CT (7,10,11). This was supported by our phantom validation study, which showed that for all 5 DECT attenuation parameters, in particular DEI, CPP detectability improved with increasing synthetic CPP crystal concentration.…”

“…The present study addressed one of the issues recently raised by the first clinical use of DECT in CPPD (7,(9)(10)(11): does early calcium crystal deposition alter DECT attenuation characteristics in menisci and articular cartilage prior to the appearance of detectable chondrocalcinosis by conventional CT? In this study, with a large enough sample size to detect clinically relevant changes in DECT attenuation characteristics, we found that with currently available DECT technology (7), the answer was no.…”

Imaging of Joints and Bones in Autoinflammation

“…The use of DECT in the diagnosis of CPPD remains controversial. Although in vitro and in vivo studies show an encouragingly high capacity for differentiation between different calcium species [ 47 , 48 , 49 ], evidence of added diagnostic value of DECT vs. conventional CT remains sparse [ 50 , 51 ]. However, DECT may be a valuable tool for strengthening the understanding of the development of specific patterns of arthropathy in CPPD as it can be used to non-invasively detect tissue remodeling [ 52 ].…”

Comparison of ultrasound attenuation by calcium pyrophosphate, hydroxyapatite and monosodium urate crystals: a proof-of-concept study

“…These specific concentrations were selected to replicate the X-ray attenuation characteristics of those crystals when imaged by conventional radiography, CT and dual-energy CT in vivo (figure 1). 6 The density of the agar-based lipogel background was intentionally increased to mimic the X-ray attenuation of hyaline cartilage (ie, 100–120 HU at 120 kVp). Each crystal suspension was removed from its Eppendorf tube and placed in a plastic container filled with US gel, next to the control (ie, crystal-free background) calibration phantom.…”

“…(A) Conventional radiography, (B) CT and (C) ultrasound (US) of the various synthetic crystal suspensions with known increasing (from left to right in A, arrow; and from top to bottom in C) concentrations of calcium pyrophosphate (CPP) (26–109 mg/mL; red in B), hydroxyapatite (HA) (31–153 mg/mL; blue in B) and monosodium urate (MSU) (90–500 mg/mL, green in B). These specific concentration ranges were selected to replicate the X-ray attenuation characteristics of those crystals in vivo 6. the dashed line represents the crystal-free (0 mg/mL) agar-based lipogel background for reference.…”