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 (Z _eff). 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 Z _eff.

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 Z _eff (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 Z _eff (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.

Keywords: Raman spectroscopy; basic calcium phosphate; calcium hydroxyapatite; calcium pyrophosphate; crystal-associated arthropathies; dual-energy computed tomography.

Figure 1.

Average Raman spectra, with characteristic marker bands, of both synthetic and biological basic calcium phosphate (BCP), most notably calcium hydroxyapatite (HA) and carbonate apatite, and calcium pyrophosphate (CPP) crystals.

Figure 2.

Comparison of dual-energy computed tomography (DECT) attenuation parameters between synthetic calcium hydroxyapatite (HA) and calcium pyrophosphate (CPP) crystal calibration phantoms at two known equal concentrations (50 and 200 mg/cm³): (A) dual-energy index (DEI), (B) electron density (Rho), and (C) effective atomic number (Z_eff).

Figure 3.

Dual-energy computed tomography (DECT) scans (A, D, shoulder, central/highest-density portion; B, E, shoulder, peripheral/lower-density portion; C, F, knee) and DECT attenuation parameters (G–I) of basic calcium phosphate (BCP) compared with calcium pyrophosphate (CPP) calcification types. Conventional grayscale CT images (A–C) with corresponding color-coded Rho/Z overlay DECT images (D–F) post-processed using proprietary Rho/Z software. Comparison of dual-energy index (DEI, G), electron density (Rho, H), and effective atomic number (Z_eff, I) in regions of interest encompassing BCP (both central and peripheral portions) and CPP calcifications.

Figure 4.

Receiver operating characteristic (ROC) curves show the accuracy of dual-energy index (DEI, dotted line) and effective atomic number (Z_eff, dashed line) in distinguishing between basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystal deposition in and around joints.