Bone structure determined by HR-MDCT does not correlate with micro-CT of lumbar vertebral biopsies: a prospective cross-sectional human in vivo study.

BACKGROUND: Osteoporosis is characterized by a deterioration of bone structure and quantity that leads to an increased risk of fractures. The primary diagnostic tool for the assessment of the bone quality is currently the dual-energy X-ray absorptiometry (DXA), which however only measures bone quantity. High-resolution multidetector computed tomography (HR-MDCT) offers an alternative approach to assess bone structure, but still lacks evidence for its validity in vivo. The objective of this study was to assess the validity of HR-MDCT for the evaluation of bone architecture in the lumbar spine. METHODS: We conducted a prospective cross-sectional study to compare the results of preoperative lumbar HR-MDCT scans with those from microcomputed tomography (µCT) analysis of transpedicular vertebral body biopsies. For this purpose, we included patients undergoing spinal surgery in our orthopedic department. Each patient underwent preoperative HR-MDCT scanning (L1-L4). Intraoperatively, transpedicular biopsies were obtained from intact vertebrae. Micro-CT analysis of these biopsies was used as a reference method to assess the actual bone architecture. HR-MDCT results were statistically analyzed regarding the correlation with results from µCT. RESULTS: Thirty-four patients with a mean age of 69.09 years (± 10.07) were included in the study. There was no significant correlation for any of the parameters (bone volume/total volume, trabecular separation, trabecular thickness) between µCT and HR-MDCT (bone volume/total volume: r = - 0.026 and p = 0.872; trabecular thickness: r = 0.074 and r = 6.42; and trabecular separation: r = - 0.18 and p = 0.254). CONCLUSION: To our knowledge, this is the first study comparing in vivo HR-MDCT with µCT analysis of vertebral biopsies in human patients. Our findings suggest that lumbar HR-MDCT is not valid for the in vivo evaluation of bone architecture in the lumbar spine. New diagnostic tools for the evaluation of osteoporosis and preoperative orthopedic planning are urgently needed.

Bone mineral density assessment using iterative reconstruction compared with quantitative computed tomography as the standard of reference.

This study examines the influence of iterative reconstruction on bone mineral density (BMD) measurement by comparison with standard quantitative computed tomography (QCT; reference) and two other protocols based on filtered back projection. Ten human cadaver specimens of the lumbar spine with a hydroxyapatite calibration phantom underneath, were scanned with 4 protocols: 1. standard QCT, 2. volume scan with FBP, 3. helical scan with FBP, and 4. helical scan with IR (Adaptive Iterative Dose Reduction 3D (AIDR3D)). Radiation doses were recorded as CT dose index (CTDIvol) and BMD, signal-to-noise and contrast-to-noise ratio were calculated. Mean hydroxyapatite concentration (HOA) did not differ significantly between protocols, ranging from 98.58 ± 31.09 mg cm3 (protocol 4) to 100.47 ± 30.82 mg cm3 (protocol 2). Paired sample correlations of HOA values for protocol 4 and protocols 1, 2 and 3 were nearly perfect with coefficients of 0.980, 0.979 and 0.982, respectively (p < 0.004). CTDIvol were 7.50, 5.00, 6.82 (±2.03) and 1.72 (±0.50) mGy for protocols 1, 2, 3 and 4 respectively. Objective image quality was highest for protocol 4. The use of IR for BMD assessment significantly lowers radiation exposure compared to standard QCT and protocols with FBP while not degrading BMD measurement.

Reviving the dinosaur: virtual reconstruction and three-dimensional printing of a dinosaur vertebra.

PURPOSE: To demonstrate the feasibility of using computed tomography (CT) to confirm the identity of an unprepared fossil and to use the CT dataset to separate the fossilized bone from its surrounding sediment matrix and produce a three-dimensional (3D) print. MATERIALS AND METHODS: The examined object was a plaster jacket containing an unprepared fossil. CT was performed with a 320-section multidetector unit. A marching cube-based method was used to transform the voxel CT dataset into triangle-based, editable geometry. Then, a comprehensive postprocessing step was performed to isolate the geometry of the vertebra from its surrounding fossilized matrix. Finally, the resulting polygon mesh describing only the vertebra was used for a physical 3D reconstruction by using a selective laser sintering machine. RESULTS: The CT examination provided enough data to assign the fossil to the genus Plateosaurus. In addition, much valuable information about the fossil has been gained-in particular the visualization of multiple fractures and the destruction of the anterior rim of the vertebral body. Finally, the results show that the 3D print generated, including the fractures and the anterior destruction, may be considered an accurate copy of the bone with the unprepared fossil. CONCLUSION: The authors demonstrated the feasibility and potential utility of combining CT with 3D printing, providing a nondestructive method to future paleontologists.

Prediction of bone strength by µCT and MDCT-based finite-element-models: how much spatial resolution is needed?

OBJECTIVES: Finite-element-models (FEM) are a promising technology to predict bone strength and fracture risk. Usually, the highest spatial resolution technically available is used, but this requires excessive computation time and memory in numerical simulations of large volumes. Thus, FEM were compared at decreasing resolutions with respect to local strain distribution and prediction of failure load to (1) validate MDCT-based FEM and to (2) optimize spatial resolution to save computation time. MATERIALS AND METHODS: 20 cylindrical trabecular bone specimens (diameter 12 mm, length 15-20mm) were harvested from elderly formalin-fixed human thoracic spines. All specimens were examined by micro-CT (isotropic resolution 30 µm) and whole-body multi-row-detector computed tomography (MDCT, 250 µm × 250 µm × 500 µm). The resolution of all datasets was lowered in eight steps to ~ 2,000 µm × 2000 µm × 500 µm and FEM were calculated at all resolutions. Failure load was determined by biomechanical testing. Probability density functions of local micro-strains were compared in all datasets and correlations between FEM-based and biomechanically measured failure loads were determined. RESULTS: The distribution of local micro-strains was similar for micro-CT and MDCT at comparable resolutions and showed a shift toward higher average values with decreasing resolution, corresponding to the increasing apparent trabecular thickness. Small micro-strains (εeff<0.005) could be calculated down to 250 µm × 250 µm × 500 µm. Biomechanically determined failure load showed significant correlations with all FEM, up to r=0.85 and did not significantly change with lower resolution but decreased with high thresholds, due to loss of trabecular connectivity. CONCLUSION: When choosing connectivity-preserving thresholds, both micro-CT- and MDCT-based finite-element-models well predicted failure load and still accurately revealed the distribution of local micro-strains in spatial resolutions, available in vivo (250 µm × 250 µm × 500 µm), that thus seemed to be the optimal compromise between high accuracy and low computation time.

Retrospective comparison of triple-sequence therapies in metastatic renal cell carcinoma.

BACKGROUND: The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined. OBJECTIVE: To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy. DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers. INTERVENTION: Sequence of systemic targeted treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression. RESULTS AND LIMITATIONS: Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases. CONCLUSIONS: The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.

Interrelationships between 3-T-MRI-derived cortical and trabecular bone structure parameters and quantitative-computed-tomography-derivedbone mineral density.

Recently, 3-T magnetic resonance imaging (MRI) has been introduced for bone imaging. Through higher signal-to-noise ratios, as compared to 1.5-T MRI, it promises to be a more powerful tool for the assessment of cortical and trabecular bone measures. The goal of our study was to compare MRI-derived cortical and trabecular bone measures to quantitative computed tomography (QCT)-derived bone mineral density (BMD). Using 3-T MRI in 51 postmenopausal women, apparent (app.) measures of bone volume/total volume, trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation were derived at the distal radius, distal tibia and calcaneus. Cortical thickness (Ct.Th) was calculated at the distal radius and distal tibia. These measures were compared to QCT-derived BMD of the spine, hip and radius. Significant correlations ((*)P<.05; (**)P<.001; (***)P<.0001) were found between spine BMD- and MRI-derived Ct.Th (r(radius)=.55, (*)P<.05; r(tibia)=.67, (***)P<.0001) and app. Tb.N (r(radius)=.33, (*)P<.05; r(tibia)=.35, (*)P<.05) at the radius and tibia. Furthermore, within the first 10 mm at the radius, an inverse correlation for Ct.Th and app. BV/TV (r(6mm)=-.56, P<.001; r(10mm)=-.36, P<.05) and app. Tb.Th (r(6mm)=-.54, P<.001; r(10mm)=-.41, P<.05) was found.

Three-dimensional distribution of trabecular bone density and cortical thickness in the distal humerus.

BACKGROUND: One major barrier to osteosynthesis in distal humeral fractures is poor bone quality. This study was an attempt to measure the bone quality in the distal humerus. METHODS: We measured the distribution of total bone mineral density (BMD), trabecular BMD (tBMD), and cortical thickness (CTh) in the distal humerus using peripheral quantitive computed tomography. Four slices in the infracondylar, supracondylar, and distal disphyseal regions of 25 human cadaver humeri were investigated. RESULTS: Total BMD decreased continuously from the distal diaphysis to the trochlea. Within the infracondylar region, the capitellum was the region of lowest tBMD and CTh (P < .001). Measurements in anterior regions were higher than in most others (P < .001). The tBMD of the medial column in the infracondylar and supracondylar regions was 31% and 36% higher vs the lateral column (P < .001). The medial column had an average 22% higher CTh in the supracondylar and 38% higher CTh in distal diaphyseal regions vs the lateral sides (P < .001). CONCLUSIONS: Distal humeral bone properties vary widely, providing stronger bone stock on the medial side. This may improve understanding of implant failure and techniques in surgical treatment.

Accessory navicular bone: when ankle pain does not originate from the ankle.

A young girl suffering from ankle pain occurring after gymnastics classes was referred to the rheumatology department by an orthopedic surgeon because a rheumatological condition was suspected to cause her symptoms. MRI was useful in pointing to the correct diagnosis of accessory navicular bone (AN). The morphological classification of ANs is discussed and the imaging modalities for diagnosis are presented.

Diffraction enhanced imaging of articular cartilage and comparison with micro-computed tomography of the underlying bone structure.

The goal of this study was to explore the role of diffraction enhanced X-ray imaging (DEI) for assessing changes in osteoarthritic cartilage and correlating the findings with concurrent changes in the underlying bone imaged using micro-computed tomography (microCT). DEI was used to image femoral head specimens at various beam energies. DEI utilizes a monochromatic, highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction. This provides images of very high contrast, with the rejection of X-ray scatter. The underlying bone was imaged using microCT and measures quantifying the bone structure were derived. Confirmation of cartilage degeneration was obtained from histology and polarized light microscopy. DEI allowed the visualization of articular cartilage and reflected the fibrillations and fissures in tissues from degenerated joints. The trabecular bone underlying the most degenerated articular cartilage showed increased bone volume fraction and more plate-like characteristics, compared with that underlying normal appearing cartilage. The histology and polarized light microscopy images reflected the DEI based features of cartilage architecture. These data reflect the ability of X-ray based emerging technologies to depict cartilage-bone interactions in joint degeneration.

X-ray detection of structural orientation in human articular cartilage.

OBJECTIVE: To determine the feasibility of detecting the structural orientation in cartilage with Diffraction Enhanced X-Ray Imaging. DESIGN: Human tali and femoral head specimens were Diffraction Enhanced X-Ray Imaged (DEI) at the SYRMEP beamline at Elettra at various energy levels to detect the architectural arrangement of collagen within cartilage. DEI utilizes a monochromatic and highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction. This provides images of very high contrast, and with the rejection of X-ray scatter. RESULTS: DEI allowed the visualization of articular cartilage and a structural orientation, resembling arcades, within. CONCLUSION: Our diffraction enhanced images represent the first radiographic detection of the structural orientation in cartilage. Our data are in line with previous studies on the structural organization of joint cartilage. They confirm the model of a vaulting system of collagen fiber bundles interrupted by proteoglycan aggregates.

MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens.

Although trabecular bone structure has been evaluated, variation with knee compartment and depth from joint surface is not completely understood. Cadaver knees were evaluated with microcomputed tomography analysis for these variations. Objective differences were compared between: medial vs. lateral compartments; femoral vs. tibial bone; and normal vs. arthritic knees. Depth dependent changes in the parameters were observed for the first 6 mm of the cores in normal knees: BV/TV, Tb.N and Conn.D gradually decrease, while Tb.Sp and SMI increase. In the first 6 mm of the normal tibia BV/TV, Tb.N, and Tb.Th are greater than in the femur on both the medial and lateral compartments while Tb.Sp, SMI, and Conn.D are lower. The medial compartment values for BV/TV, Tb.N, Tb.Th and Conn.D are generally greater than for the lateral in both the femur and tibia while Tb.Sp and SMI are lower. In comparison of normal vs. arthritic knees significant differences are observed in the first 6 mm of the medial tibia. With arthritis BV/TV and Tb.Th are lower, while SMI and Tb.Sp are higher. Tb.N and Conn.D show no statistically significant difference. The bone structure variations are, thus, most prominent in the first 6 mm of depth and medial compartment bone is generally more structurally sound than lateral. Severely arthritic bone changes are most prominent in the medial compartment of the tibia and bone structure is less sound in severe arthritis.

Micro-computed tomography evaluation of trabecular bone structure on loaded mice tail vertebrae.

STUDY DESIGN: A micro-computed tomography (CT) study of the trabecular bone structure on loaded mice tail vertebral bodies was conducted. OBJECTIVE: To depict and characterize changes in the trabecular bone structure of mice tail vertebral bodies after in vivo application of static compressive load. SUMMARY OF BACKGROUND DATA: Static compressive loading leads to significant structural changes in murine tail intervertebral discs, such as disorganization of the anulus fibrosus, increase in apoptosis, and associated loss of cellularity. Wolff's Law suggests that alterations in spinal loading will also influence the architecture of the adjacent vertebral bodies. Because of biomechanical and biologic interdependencies between the disc and vertebra, these tissues should be considered simultaneously when investigating the etiology of degenerative spinal conditions. METHODS: Mice tail discs between the ninth and 10th caudal vertebrae were compressed in vivo for 7 days with static axial loads using external fixators. Micro-CT scans of the vertebral bodies were performed at an isotropic resolution of 18 microm, to obtain trabecular bone structural parameters. Random effects models were used to evaluate statistical significance of these parameters in different compressed conditions. RESULTS: With loading, the connectivity density of the trabecular network increases significantly. After a period of in vivo recovery on load removal, the trabeculae become more rod-like; corresponding changes such as disorganization of the anulus fibrosus and loss of nuclear and inner-anular cellularity are also seen. CONCLUSIONS: In vivo compressive loading leads to significant architectural changes within vertebral bodies. These observations may be helpful in understanding the pathologic processes and the chronology of degenerative spinal conditions.

Local differences in the trabecular bone structure of the proximal femur depicted with high-spatial-resolution MR imaging and multisection CT.

RATIONALE AND OBJECTIVES: The authors performed this study to investigate structural variations in the trabecular bone of the proximal femur at high-resolution magnetic resonance (MR) imaging and high-resolution multisection computed tomography (CT). MATERIALS AND METHODS: Bone mineral density (BMD) was measured in 36 proximal human femur specimens by using dual x-ray absorptiometry. High-resolution MR imaging was performed at 1.5 T with an in-plane spatial resolution of 0.195 x 0.195 mm and a section thickness of 0.3 and 0.9 mm. Multisection CT was performed with an ultra-high-resolution protocol; images were obtained with an in-plane spatial resolution of 0.25 mm and a section thickness of 1 mm. In a subset of these specimens, micro CT was performed with an isotropic spatial resolution of 30 microm. Identical regions of interest (ROIs) were used to analyze images obtained with MR imaging, multisection CT, and micro CT. Trabecular bone structural parameters were obtained, and the parameters from the individual imaging modalities and BMD were correlated. RESULTS: Significant differences concerning the trabecular microarchitecture between the individual ROIs were demonstrated with multisection CT and MR imaging. A number of the correlations between structural parameters derived with multisection CT, MR imaging, micro CT, and BMD measurements were significant. For MR imaging, threshold technique and section thickness had an effect on structural parameters. CONCLUSION: Structural parameters obtained in the proximal femur with multisection CT and high-resolution MR imaging show regional differences. These techniques may be useful for depicting the trabecular architecture in the diagnosis of osteoporosis.