Dual-Layer Spectral-Computed Tomography Enhances the Separability of Calcium-Based Implant Material from Bone: An Ex Vivo Quantitative Imaging Study.

Local treatment of bone loss with an injection of a resorbable, calcium-based implant material to replace bone has a long history of clinical use. The in vivo discrimination of changes in bone versus implant is challenging with standard computed tomography (CT). However, spectral-CT techniques enable the separation between tissues of similar densities but different chemical compositions. Dual-layer spectral-CT imaging and postprocessing analysis methods were applied to investigate the separability of AGN1 (a triphasic calcium-based implant) and bone after AGN1 injection in n = 10 male cadaveric femurs ex vivo. Using the area under the curve (AUC) from receiver-operating characteristic (ROC) analyses, the separability of AGN1 from bone was assessed for AGN1 (postoperatively) versus compact and versus femoral neck cancellous bone (both preoperatively). CT techniques included conventional Hounsfield (HU) and density-equivalent units (BMD, mg hydroxyapatite [HA]/cm3 ) and spectral-CT measures of effective atomic number (Zeff) and electron density (ED). The samples had a wide range of femoral neck BMD (55.66 to 241.71 mg HA/cm3 ). At the injection site average BMD, HU, Zeff, and ED increased from 69.5 mg HA/cm3 , 109 HU, 104.38 EDW, and 8.30 Zeff in the preoperative to 1233 mg HA/cm3 , 1741 HU, 181.27 EDW, and 13.55 Zeff in the postoperative CT scan, respectively. For compact bone at the femoral shaft the preoperative values were 1124.15 mg HA/cm3 , 1648 HU, 177 EDW, and 13.06 Zeff and were maintained postoperatively. Zeff showed substantially sharper distributions and significantly greater separability compared to ED, BMD, and HU (all p < 0.002, for both regions) with average AUCs for BMD, HU, ED, and Zeff of 0.670, 0.640, 0.645, and 0.753 for AGN1 versus compact and 0.996, 0.995, 0.994, and 0.998 for AGN1 versus femoral neck cancellous sites, respectively. Spectral-CT permits better discrimination of calcium-based implants like AGN1 from bone ex vivo. Our results warrant application of spectral-CT in patients undergoing procedures with similar implants. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dose-efficient assessment of trabecular microstructure using ultra-high-resolution photon-counting CT.

Photon-counting (PC) detectors for clinical computed tomography (CT) may offer improved imaging capabilities compared to conventional energy-integrating (EI) detectors, e.g. superior spatial resolution and detective efficiency. We here investigate if PCCT can reduce the administered dose in examinations aimed at quantifying trabecular bone microstructure. Five human vertebral bodies were scanned three times in an abdomen phantom (QRM, Germany) using an experimental dual-source CT (Somatom CounT, Siemens Healthineers, Germany) housing an EI detector (0.60 mm pixel size at the iso-center) and a PC detector (0.25 mm pixel size). A tube voltage of 120 kV was used. Tube current-time product for EICT was 355 mAs (23.8 mGy CTDI32 cm). Dose-matched UHR-PCCT (UHRdm, 23.8 mGy) and noise-matched acquisitions (UHRnm, 10.5 mGy) were performed and reconstructed to a voxel size of 0.156 mm using a sharp kernel. Measurements of bone mineral density (BMD) and trabecular separation (Tb.Sp) and Tb.Sp percentiles reflecting the different scales of the trabecular interspacing were performed and compared to a gold-standard measurement using a peripheral CT device (XtremeCT, SCANCO Medical, Switzerland) with an isotropic voxel size of 0.082 mm and 6.6 mGy CTDI10 cm. The image noise was quantified and the relative error with respect to the gold-standard along with the agreement between CT protocols using Lin's concordance correlation coefficient (rCCC) were calculated. The Mean ±â€¯StdDev of the measured image noise levels in EICT was 109.6 ±â€¯3.9 HU. UHRdm acquisitions (same dose as EICT) showed a significantly lower noise level of 78.6 ±â€¯4.6 HU (p = 0.0122). UHRnm (44% dose of EICT) showed a noise level of 115.8 ±â€¯3.7 HU, very similar to EICT at the same spatial resolution. For BMD the overall Mean ±â€¯StdDev for EI, UHRdm and UHRnm were 114.8 ±â€¯28.6 mgHA/cm3, 121.6 ±â€¯28.8 mgHA/cm3 and 121.5 ±â€¯28.6 mgHA/cm3, respectively, compared to 123.1 ±â€¯25.5 mgHA/cm3 for XtremeCT. For Tb.Sp these values were 1.86 ±â€¯0.54 mm, 1.80 ±â€¯0.56 mm and 1.84 ±â€¯0.52 mm, respectively, compared to 1.66 ±â€¯0.48 mm for XtremeCT. The ranking of the vertebrae with regard to Tb.Sp data was maintained throughout all Tb.Sp percentiles and among the CT protocols and the gold-standard. The agreement between protocols was very good for all comparisons: UHRnm vs. EICT (BMD rCCC = 0.97; Tb.Sp rCCC = 0.998), UHRnm vs. UHRdm (BMD rCCC = 0.998; Tb.Sp rCCC = 0.993) and UHRdm vs. EICT (BMD rCCC = 0.97; Tb.Sp rCCC = 0.991). Consequently, the relative RMS-errors from linear regressions against the gold-standard for EICT, UHRdm and UHRnm were very similar for BMD (7.1%, 5.2% and 5.4%) and for Tb.Sp (3.3%, 3.3% and 2.9%), with a much lower radiation dose for UHRnm. Short-term reproducibility for BMD measurements was similar and below 0.2% for all protocols, but for Tb.Sp showed better results for UHR (about 1/3 of the level for EICT). In conclusion, CT with UHR-PC detectors demonstrated lower image noise and better reproducibility for assessments of bone microstructure at similar dose levels. For UHRnm, radiation exposure levels could be reduced by 56% without deterioration of performance levels in the assessment of bone mineral density and bone microstructure.

Improved accuracy in the assessment of vertebral cortical thickness by quantitative computed tomography using the Iterative Convolution OptimizatioN (ICON) method.

Vertebral whole bone strength is substantially affected by cortical bone properties. Disease and therapy may affect cancellous and cortical bone differently. Unlike Dual X-ray Absorptiometry (DXA), Quantitative Computed Tomography (QCT) permits selective assessment of cortical and cancellous bone, but image quality limits the accuracy. We present an image processing method specifically adopted to thin cortices that substantially improves accuracy. Ten human vertebrae embedded in epoxy resin were imaged using clinical QCT and High-Resolution QCT (HR-QCT) protocols, both acquired on a clinical whole body CT scanner, whereas high resolution peripheral QCT (HR-pQCT) was used as gold standard. Microstructural variables and BMD were calculated using in-house software StructuralInsight for QCT and HR-QCT and the manufacturer's µCT evaluation software for HR-pQCT. An adjusted measure, a deconvolved cortical thickness (dcCt.Th), corrected for partial volume effects, was derived applying the new Iterative Convolution OptimizatioN (ICON) method. Direct measurements of cortical thickness (Ct.Th) showed substantial overestimation with mean ±â€¯standard deviation of 1.8 ±â€¯0.5 mm for QCT and 1.5 ±â€¯0.3 mm for HR-QCT compared to 0.37 ±â€¯0.07 mm using HR-pQCT. Correlations of both QCT (r2 = 0.05, p > 0.5.) and HR-QCT (r2 = 0.38, p = 0.060) with the gold standard HR-pQCT were not significant. Also QCT-based BMD and BMC as well as HR-QCT-based BMD did not show a significant correlation with the gold standard approach. Only HR-QCT-based BMC showed a modest correlation (r2 = 0.59, p = 0.01) After applying ICON corrections, dcCt.Th resulted in 0.52 ±â€¯0.09 mm for QCT and 0.43 ±â€¯0.07 mm for HR-QCT, both significantly correlated to HR-pQCT (r2 = 0.75, p = 0.0012 and r2 = 0.93, p < 0.0001, respectively). The average overestimation bias of Ct.Th was reduced from (402 ±â€¯157)% to (45 ±â€¯17)% for QCT and from (330 ±â€¯69)% to (19 ±â€¯8)% for HR-QCT. Due to inaccurate segmentation uncorrected QCT-based Ct.Th measures as well as BMD and BMC showed no correlation to HR-pQCT and thus such bias cortical data can be misleading. The application of ICON reduced random overestimation bias to about 50 µm and 20 µm for QCT and HR-QCT, respectively, leading to a recovery of a significant correlation with the reference data of HR-pQCT. This reveals the potential for fairly accurate assessment of cortical thickness, allowing to better characterize cortical mechanical competence. These results warrant testing of the performance in vivo.

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling.

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T12 (T11 if T12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (-15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (-21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (-27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R2 = 0.57, yield force: R2 = 0.59, work to yield: R2 = 0.50, p < 0.001), BV/TV (stiffness: R2 = 0.56, yield force: R2 = 0.58, work to yield: R2 = 0.49, p < 0.001), and Tb.Sp (stiffness: R2 = 0.51, yield force: R2 = 0.53, work to yield: R2 = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research.

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography.

PURPOSE: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. METHODS: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1-1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. RESULTS: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm(3) corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. CONCLUSIONS: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.