Impact of CT reconstruction algorithm on auto-segmentation performance.

Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP). Images were created from raw projection data for 11 prostate cancer cases using FBP and nine different MBIR reconstructions (3 protocols/3 noise reduction levels) yielding 10 reconstructions/patient. Five bony structures, bladder, rectum, prostate, and seminal vesicles (SVs) were segmented using an auto-segmentation pipeline that renders 3D binary masks for analysis. Performance was evaluated for volume percent difference (VPD) and Dice similarity coefficient (DSC), using FBP as the gold standard. Nonparametric Friedman tests plus post hoc all pairwise comparisons were employed to test for significant differences (P < 0.05) for soft tissue organs and protocol/level combinations. A physician performed qualitative grading of 396 MBIR contours across the prostate, bladder, SVs, and rectum in comparison to FBP using a six-point scale. MBIR contours agreed with FBP for bony anatomy (DSC ≥ 0.98), bladder (DSC ≥ 0.94, VPD < 8.5%), and prostate (DSC = 0.94 ± 0.03, VPD = 4.50 ± 4.77% (range: 0.07-26.39%). Increased variability was observed for rectum (VPD = 7.50 ± 7.56% and DSC = 0.90 ± 0.08) and SVs (VPD and DSC of 8.23 ± 9.86% range (0.00-35.80%) and 0.87 ± 0.11, respectively). Over the all protocol/level comparisons, a significant difference was observed for the prostate VPD between BSPL1 and BSTL2 (adjusted P-value = 0.039). Nevertheless, 300 of 396 (75.8%) of the four soft tissue structures using MBIR were graded as equivalent or better than FBP, suggesting that MBIR offered potential improvements in auto-segmentation performance when compared to FBP. Future work may involve tuning organ-specific MBIR parameters to further improve auto-segmentation performance. Running title: Impact of CT Reconstruction Algorithm on Auto-segmentation Performance.

Detection of early osteoarthritis in canine knee joints 3 weeks post ACL transection by microscopic MRI and biomechanical measurement.

PURPOSE: To detect early osteoarthritis (OA) in a canine Pond-Nuki model 3 weeks after anterior cruciate ligament (ACL) transection surgery, both topographically over the medial tibial surface and depth-dependently over the cartilage thickness. METHODS: Four topographical locations on each OA and contralateral medial tibia were imaged individually by magnetic resonance imaging (MRI) at 17.6 µm transverse resolution. The quantitative MRI T2 relaxation data were correlated with the biomechanical stress-relaxation measurements from adjacent locations. RESULTS: OA cartilage was thinner than the contralateral tissue and had a lower modulus compared to the contralateral cartilage for the exterior, interior, and central medial tibia locations. Depth-dependent and topographical variations were detected in OA cartilage by a number of parameters (compressive modulus, glycosaminoglycan concentration, bulk and zonal thicknesses, T2 at 0° and 55° specimen orientations in the magnet). T2 demonstrated significant differences at varying depths between OA and contralateral cartilage. CONCLUSION: ACL transection caused a number of changes in the tibial cartilage at 3 weeks after the surgery. The characteristics of these changes, which are topographic and depth-dependent, likely reflect the complex degradation in this canine model of OA at the early developmental stage.

Topographical and depth-dependent glycosaminoglycan concentration in canine medial tibial cartilage 3 weeks after anterior cruciate ligament transection surgery-a microscopic imaging study.

BACKGROUND: Medical imaging has become an invaluable tool to diagnose damage to cartilage. Depletion of glycosaminoglycans (GAG) has been shown to be one of the early signs of cartilage degradation. In order to investigate the topographical changes in GAG concentration caused by the anterior cruciate ligament transection (ACLT) surgery in a canine model, microscopic magnetic resonance imaging (µMRI) and microscopic computed tomography (µCT) were used to measure the GAG concentration with correlation from a biochemical assay, inductively coupled plasma optical emission spectroscopy (ICP-OES), to understand where the topographical and depth-dependent changes in the GAG concentration occur. METHODS: This study used eight knee joints from four canines, which were examined 3 weeks after ACLT surgery. From right (n=3) and left (n=1) medial tibias of the ACLT and the contralateral side, two ex vivo specimens from each of four locations (interior, central, exterior and posterior) were imaged before and after equilibration in contrast agents. The cartilage blocks imaged using µMRI were approximately 3 mm × 5 mm and were imaged before and after eight hours submersion in a gadolinium (Gd) contrast agent with an in-plane pixel resolution of 17.6 µm2 and an image slice thickness of 1 mm. The cartilage blocks imaged using µCT were approximately 2 mm × 1 mm and were imaged before and after 24 hours submersed in ioxaglate with an isotropic voxel resolution of 13.4 µm3. ICP-OES was used to quantify the bulk GAG at each topographical location. RESULTS: The pre-contrast µMRI and µCT results did not demonstrate significant differences in GAG between the ACLT and contralateral cartilage at all topographical locations. The post-contrast µMRI and µCT results demonstrated topographically similar significant differences in GAG concentrations between the ACLT and contralateral tibia. Using µMRI, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (54.0±3.6; 70.4±4.3; P=0.001) and interior (54.9±5.9; 71.0±5.9; P=0.029) demonstrated significant differences, but not for the central (61.0±12.0; 67.4±7.2; P=0.438) or posterior (61.6±6.3; 70.3±4.4; P=0.097) locations. Using µCT, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (68.8±0.4; 87.7±4.1; P=0.023) and interior (60.5±9.1; 82.6±8.7; P=0.039) demonstrated significant differences, but not for the central (53.5±5.5; 59.1±25.6; P=0.684) or posterior (52.3±6.2; 61.5±12.7; P=0.325) locations. The depth-dependent GAG (mg/mL) profiles showed significant differences in µMRI for the transitional zone (TZ) [exterior (28.1±4.7; 47.0±8.6; P=0.01) and interior (32.6±4.8; 43.8±8.7; P=0.025)], radial zone (RZ) 1 [exterior (49.6±4.8; 71.5±5.8; P=0.001) and interior (49.4±7.4; 66.7±6.8; P=0.041)], and RZ 2 [exterior (74.9±4.7; 91.8±2.9; P=0.001) and interior (77.1±6.0; 94.8±4.5; P=0.015)], and in µCT for the superficial zone (SZ) [interior (20.6±1.2; 40.4±5.4; P=0.004)], TZ [exterior (45.6±12.0; 61.8±0.5; P=0.049) and interior (36.3±11.7; 60.8±2.0; P=0.019)], and RZ 1 [exterior (61.1±4.1; 85.3±5.6; P=0.039) and interior (53.9±4.9; 78.0±5.1; P=0.041)] for the ACLT and contralateral, respectively. ICP-OES measured significant differences in GAG were found for the exterior (42.1±19.6; 65.3±16.2; P=0.017), central (43.4±4.4; 65.3±10.6; P=0.0111), and interior (46.8±5.6; 61.7±7.3; P=0.0445) but not for the posterior (52.6±12.1; 59.0±2.6; P=0.9252) medial tibia locations compared for the ACLT and contralateral, respectively. CONCLUSIONS: The detection and correlation between the three techniques show a topographic depth-dependency on the initial GAG loss in injured cartilage. This topographic and high resolution investigation of ACLT cartilage demonstrated the potential of using µMRI and µCT to study and help diagnose cartilage with very early stages of osteoarthritis.

Meniscus Induced Cartilaginous Damage and Non-linear Gross Anatomical Progression of Early-stage Osteoarthritis in a Canine Model.

BACKGROUND: The predictable outcome of the anterior cruciate ligament transection (ACLT) canine model, and the similarity to naturally occurring osteoarthritis (OA) in humans, provide a translatable method for studying OA. Still, evidence of direct meniscus-induced cartilaginous damage has not been identified, and gross-anatomical blinded scoring of early-stage OA has not been performed. OBJECTIVE: A gross anatomical observation and statistical analysis of OA progression to determine meniscus induced cartilaginous damage, to measure the macroscopic progression of OA, and to address matters involving arthroscopic and surgical procedures of the knee. METHOD: Unblinded assessment and blinded scoring of meniscal, tibial, femoral, and patellar damage were performed for control and at four time points following unilateral ACLT: 3-week (N=4), 8-week (N=4), 12-week (N=5), and 25-week (N=4). Mixed-model statistics illustrates damage (score) progression; Wilcoxon rank-sum tests compared time-point scores; and Wilcoxon signed-rank tests compared ACLT and contralateral scores, and meniscus and tibia scores. RESULT: Damage was manifest first on the posterior aspect of the medial meniscus and subsequently on the tibia and femur, implying meniscal damage can precede, coincide with, and aggravate cartilage damage. Damage extent varied chronologically and was dependent upon the joint component. Meniscal damage was evident at 3 weeks and progressed through 25-weeks. Meniscal loose bodies corresponded to tibial cartilage damage location and extent through 12 weeks, followed by cartilage repair activity after complete meniscal degeneration. CONCLUSION: This study provides additional information for understanding OA progression, identifying OA biomarkers, and arthroscopic and meniscectomy procedures.

Depth-Dependent Glycosaminoglycan Concentration in Articular Cartilage by Quantitative Contrast-Enhanced Micro-Computed Tomography.

OBJECTIVE: A quantitative contrast-enhanced micro-computed tomography (qCECT) method was developed to investigate the depth dependency and heterogeneity of the glycosaminoglycan (GAG) concentration of ex vivo cartilage equilibrated with an anionic radiographic contrast agent, Hexabrix. DESIGN: Full-thickness fresh native (n = 19 in 3 subgroups) and trypsin-degraded (n = 6) articular cartilage blocks were imaged using micro-computed tomography (µCT) at high resolution (13.4 µm(3)) before and after equilibration with various Hexabrix bathing concentrations. The GAG concentration was calculated depth-dependently based on Gibbs-Donnan equilibrium theory. Analysis of variance with Tukey's post hoc was used to test for statistical significance (P < 0.05) for effect of Hexabrix bathing concentration, and for differences in bulk and zonal GAG concentrations individually and compared between native and trypsin-degraded cartilage. RESULTS: The bulk GAG concentration was calculated to be 74.44 ± 6.09 and 11.99 ± 4.24 mg/mL for native and degraded cartilage, respectively. A statistical difference was demonstrated for bulk and zonal GAG between native and degraded cartilage (P < 0.032). A statistical difference was not demonstrated for bulk GAG when comparing Hexabrix bathing concentrations (P > 0.3214) for neither native nor degraded cartilage. Depth-dependent GAG analysis of native cartilage revealed a statistical difference only in the radial zone between 30% and 50% Hexabrix bathing concentrations. CONCLUSIONS: This nondestructive qCECT methodology calculated the depth-dependent GAG concentration for both native and trypsin-degraded cartilage at high spatial resolution. qCECT allows for more detailed understanding of the topography and depth dependency, which could help diagnose health, degradation, and repair of native and contrived cartilage.

Quantitative determination of morphological and territorial structures of articular cartilage from both perpendicular and parallel sections by polarized light microscopy.

In order to investigate the three-dimensional structure of the collagen fibrils in articular cartilage, full-thickness canine humeral cartilage was microtomed into perpendicular sections that included both the articular surface and the subchondral bone and approximately 100 successive parallel sections that were each 6 microm thick and from a different cartilage depth. Each section was imaged using polarized light microscopy with a 5x objective (2.0 microm pixel size), generating two quantitative images (angle and retardation). Selected sections were also imaged using a 40x objective (0.25 microm pixel size). At an increased depth from the articular surface, the angle and retardation results in the perpendicular sections showed the well-known 90 degrees change in fibril orientation between the surface and the deep cartilage. In contrast, the retardation results of the parallel sections decreased from the articular surface and remained approximately 0 through most of the radial zones, while the angle results of the parallel sections only changed about 30 degrees. The territorial matrix morphology surrounding 61 chondrocyte clusters was quantified by its length, aspect ratio, and orientation. The cellular clusters in the surface cartilage were ellipsoidal in both parallel and perpendicular sections. In the radial zone, the cellular clusters were oriented in vertical columns in the perpendicular sections and as circular groupings in the parallel sections. This orthogonal imaging technique could provide a better understanding of the three-dimensional territorial and interterritorial fibrils in articular cartilage, the disturbance of which could signify the onset of degenerative cartilage diseases such as osteoarthritis.

Depth-dependent anisotropies of amides and sugar in perpendicular and parallel sections of articular cartilage by Fourier transform infrared imaging.

Full thickness blocks of canine humeral cartilage were microtomed into both perpendicular sections and a series of 100 parallel sections, each 6 µm thick. Fourier transform infrared (IR) imaging was used to image each tissue section eleven times under different IR polarizations (from 0° to 180° polarization states in 20° increments and with an additional 90° polarization), at a spatial resolution of 6.25 µm and a wavenumber step of 8 cm⁻¹. With increasing depth from the articular surface, amide anisotropies increased in the perpendicular sections and decreased in the parallel sections. Both types of tissue sectioning identified a 90° difference between amide I and amide II in the superficial zone (SZ) of cartilage. The fibrillar distribution in the parallel sections from the SZ was shown to not be random. Sugar had a weak but recognizable anisotropy in the upper part of the radial zone (RZ) in the perpendicular sections. The depth-dependent anisotropic data were fitted with a theoretical equation that contained three signature parameters, which illustrate the arcade structure of collagens with the aid of a fibril model. Fourier-transform IR imaging of both perpendicular and parallel sections provides the possibility of determining the three-dimensional macromolecular structures in articular cartilage. Being sensitive to the orientation of the macromolecular structure in healthy articular cartilage aids the prospect of detecting the early onset of the tissue degradation that may lead to pathological conditions such as osteoarthritis.