Ioxaglate Versus IoDixanol for the Prevention of Contrast-Induced Nephropathy: The IDPC Trial.

BACKGROUND: Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE). AIMS: We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients. METHODS: This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs. iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration. RESULTS: A total of 2,268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs. low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P =.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs. 29 (2.6%) in the low-osmolarity group (P =.4). CONCLUSION: Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.

Cationic Carrier Mediated Delivery of Anionic Contrast Agents in Low Doses Enable Enhanced Computed Tomography Imaging of Cartilage for Early Osteoarthritis Diagnosis.

Cartilage tissue exhibits early degenerative changes with onset of osteoarthritis (OA). Early diagnosis is critical as there is only a narrow time window during which therapeutic intervention can reverse disease progression. Computed tomography (CT) has been considered for cartilage imaging as a tool for early OA diagnosis by introducing radio-opaque contrast agents like ioxaglate (IOX) into the joint. IOX, however, is anionic and thus repelled by negatively charged cartilage glycosaminoglycans (GAGs) that hinders its intra-tissue penetration and partitioning, resulting in poor CT attenuation. This is further complicated by its short intra-tissue residence time owing to rapid clearance from joints, which necessitates high doses causing toxicity concerns. Here we engineer optimally charged cationic contrast agents based on cartilage negative fixed charge density by conjugating cartilage targeting a cationic peptide carrier (CPC) and multi-arm avidin nanoconstruct (mAv) to IOX, such that they can penetrate through the full thickness of cartilage within 6 h using electrostatic interactions and elicit similar CT signal with about 40× lower dose compared to anionic IOX. Their partitioning and distribution correlate strongly with spatial GAG distribution within healthy and early- to late-stage arthritic bovine cartilage tissues at 50-100× lower doses than other cationic contrast agents used in the current literature. The use of contrast agents at low concentrations also allowed for delineation of cartilage from subchondral bone as well as other soft tissues in rat tibial joints. These contrast agents are safe to use at current doses, making CT a viable imaging modality for early detection of OA and staging of its severity.

Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo.

BACKGROUND: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. OBJECTIVES: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. STUDY DESIGN: Pre-clinical experimental study. METHODS: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = -1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. RESULTS: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. MAIN LIMITATIONS: Ex vivo study protocol and a low number of investigated joints. CONCLUSIONS: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage.

Cationic Contrast Agents for Computed Tomography of Cartilage for Early Diagnosis of Osteoarthritis.

Here we describe methods for synthesizing cationic contrast agents for computed tomography (CT) of cartilage for early diagnosis of tissue degeneration. CT imaging of soft tissues like cartilage is possible only if radio-opaque contrast agents (e.g., ioxaglate) can penetrate through the full thickness of tissue in sufficient concentrations. Ioxaglate (IOX), however, is anionic and is repelled by the negatively charged cartilage matrix resulting in poor CT attenuation. Here we demonstrate cartilage penetrating cationic contrast agents using multi-arm Avidin (mAv) conjugated to ioxaglate (mAv-IOX). mAv-IOX rapidly penetrates through the full thickness of cartilage in high concentrations owing to weak-reversible nature of electrostatic interactions resulting in high CT attenuation even with low doses unlike IOX. The technology has the potential for enabling clinical CT of cartilage and other negatively charged soft tissues.

Aging does not change the compressive stiffness of mandibular condylar cartilage in horses.

OBJECTIVE: Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical properties of the temporomandibular joint (TMJ) cartilage. Hence, the aim of this study was to examine the biophysical properties (thickness, stiffness, and diffusion) of the TMJ condylar cartilage of horses of different ages and their correlation with biochemical parameters. MATERIALS AND METHODS: We measured the compressive stiffness of the condyles, after which the diffusion of two contrast agents into cartilage was measured using Contrast Enhanced Computed Tomography technique. Furthermore, the content of water, collagen, GAG, and pentosidine was analyzed. RESULTS: Contrary to our expectations, the stiffness of the cartilage did not change with age (modulus remained around 0.7 MPa). The diffusion of the negatively charged contrast agent (Hexabrix) also did not alter. However, the diffusion of the uncharged contrast agent (Visipaque) decreased with aging. The flux was negatively correlated with the amount of collagen and crosslink level which increased with aging. Pentosidine, collagen, and GAG were positively correlated with age whereas thickness and water content showed negative correlations. CONCLUSION: Our data demonstrated that aging was not necessarily reflected in the biophysical properties of TMJ condylar cartilage. The combination of the changes happening due to aging resulted in different diffusive properties, depending on the nature of the solution.

An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy.

PURPOSE: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. METHODS: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. RESULTS: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. CONCLUSION: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy

Abstract Purpose: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. Methods: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. Results: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. Conclusion: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

Nondestructive, indirect assessment of the biomechanical properties of the rat intervertebral disc using contrast-enhanced µCT.

Mechanical characterization of the intervertebral disc involves labor-intensive and destructive experimental methodology. Contrast-enhanced micro-computed tomography is a nondestructive imaging modality for high-resolution visualization and glycosaminoglycan quantification of cartilaginous tissues. The purpose of this study was to determine whether anionic and cationic contrast-enhanced micro-computed tomography of the intervertebral disc can be used to indirectly assess disc mechanical properties in an ex vivo model of disc degeneration. L3/L4 motion segments were dissected from female Lewis rats. To deplete glycosaminoglycan, samples were treated with 0 U/ml (Control) or 5 U/ml papain. Contrast-enhanced micro-computed tomography was performed following incubation in 40% Hexabrix (anionic) or 30 mg I/ml CA4+ (cationic) for 24 h (n = 10/contrast agent/digestion group). Motion segments underwent cyclic mechanical testing to determine compressive and tensile modulus, stiffness, and hysteresis. Glycosaminoglycan content was determined using the dimethylmethylene blue assay. Correlations between glycosaminoglycan content, contrast-enhanced micro-computed tomography attenuation, and mechanical properties were assessed via the Pearson correlation. The predictive accuracy of attenuation on compressive properties was assessed via repeated random sub-sampling cross validation. Papain digestion produced significant decreases in glycosaminoglycan content and corresponding differences in attenuation and mechanical properties. Attenuation correlated significantly to glycosaminoglycan content and to all compressive mechanical properties using both Hexabrix and CA4+ . Predictive linear regression models demonstrated a predictive accuracy of attenuation on compressive modulus and stiffness of 79.8-86.0%. Contrast-enhanced micro-computed tomography was highly predictive of compressive mechanical properties in an ex vivo simulation of disc degeneration and may represent an effective modality for indirectly assessing disc compressive properties. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2030-2038, 2018.

Nondestructive Assessment of Glycosaminoglycans in Engineered Cartilages Using Hexabrix-Enhanced Micro-Computed Tomography

It is very useful to evaluate the content and 3D distribution of extracellular matrix non-destructively in tissue engineering. This study evaluated the feasibility of using micro-computed tomography (µCT) with Hexabrix to measure quantitatively sulfated glycosaminoglycans (GAGs) of engineered cartilage. Rabbit chondrocytes at passage 2 were used to produce artificial cartilages in polyglycolic acid scaffolds in vitro. Engineered cartilages were incubated with Hexabrix 320 for 20 min and analyzed via µCT scanning. The number of voxels in the 2D and 3D scanning images were counted to estimate the amount of sulfated GAGs. The optimal threshold value for quantification was determined by regression analysis. The 2D µCT images of an engineered cartilage showed positive correlation with the histological image of Safranin-O staining. Quantitative data obtained with the 3D µCT images of 14 engineered cartilages showed strong correlation with sulfated GAGs contents obtained by biochemical analysis (R² = 0.883, p < 0.001). Repeated exposure of engineered cartilages to Hexabrix 320 and µCT scanning did not significantly affect cell viability, total DNA content, or the total content of sulfated GAGs. We conclude that µCT imaging using Hexabrix 320 provides high spatial resolution and sensitivity to assess the content and 3D distribution of sulfated GAGs in engineered cartilages. It is expected to be a valuable tool to evaluate the quality of engineered cartilage for commercial development in the future.

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

Murine articular cartilage morphology and compositional quantification with high resolution cationic contrast-enhanced µCT.

Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (µCT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (∼30-50 µm) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by µCT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6 µm) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution µCT imaging (3 µm voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and µCT (R2 = 0.72, p < 0.001). Cartilage degeneration-as assessed by loss in volume, thickness, and PG content-was observed in 34-week-old mice when compared to both 7- and 12-week-old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2740-2748, 2017.

Pulsed lavage cleansing of osteochondral grafts depends on lavage duration, flow intensity, and graft storage condition.

INTRODUCTION: Osteochondral allograft (OCA) transplantation is generally effective for treating large cartilage lesions. Cleansing OCA subchondral bone to remove donor marrow elements is typically performed with pulsed lavage. However, the effects of clinical and experimental parameters on OCA marrow removal by pulsed lavage are unknown. The aim of the current study was to determine the effects on marrow cleansing in human osteochondral cores (OCs) of (1) lavage duration, (2) lavage flow intensity, and (3) OC sample type and storage condition. METHODS: OCs were harvested from human femoral condyles and prepared to a clinical geometry (cylinder, diameter = 20 mm). The OCs were from discarded remnants of Allograft tissues (OCA) or osteoarthritis patients undergoing Total Knee Replacement (OCT). The experimental groups subjected to standard flow lavage for 45 seconds (430 mL of fluid) and 120 seconds (1,150 mL) were (1) OCT/FROZEN (stored at -80°C), (2) OCT/FRESH (stored at 4°C), and (3) OCA/FRESH. The OCA/FRESH group was subsequently lavaged at high flow for 45 seconds (660 mL) and 120 seconds (1,750 mL). Marrow cleansing was assessed grossly and by micro-computed tomography (µCT). RESULTS: Gross and µCT images indicated that marrow cleansing progressed from the OC base toward the cartilage. Empty marrow volume fraction (EMa.V/Ma.V) increased between 0, 45, and 120 seconds of standard flow lavage, and varied between groups, being higher after FROZEN storage (86-92% after 45-120 seconds) than FRESH storage of either OCT or OCA samples (36% and 55% after 45 and 120 seconds, respectively). With a subsequent 120 seconds of high flow lavage, EMa.V/Ma.V of OCA/FRESH samples increased from 61% to 78%. CONCLUSIONS: The spatial and temporal pattern of marrow space clearance was consistent with gradual fluid-induced extrusion of marrow components. Pulsed lavage of OCAs with consistent time and flow intensity will help standardize marrow cleansing and may improve clinical outcomes.

Accuracy of iodine quantification using dual energy CT in latest generation dual source and dual layer CT.

OBJECTIVE: To determine the accuracy of iodine quantification with dual energy computed tomography (DECT) in two high-end CT systems with different spectral imaging techniques. METHODS: Five tubes with different iodine concentrations (0, 5, 10, 15, 20 mg/ml) were analysed in an anthropomorphic thoracic phantom. Adding two phantom rings simulated increased patient size. For third-generation dual source CT (DSCT), tube voltage combinations of 150Sn and 70, 80, 90, 100 kVp were analysed. For dual layer CT (DLCT), 120 and 140 kVp were used. Scans were repeated three times. Median normalized values and interquartile ranges (IQRs) were calculated for all kVp settings and phantom sizes. RESULTS: Correlation between measured and known iodine concentrations was excellent for both systems (R = 0.999-1.000, p < 0.0001). For DSCT, median measurement errors ranged from -0.5% (IQR -2.0, 2.0%) at 150Sn/70 kVp and -2.3% (IQR -4.0, -0.1%) at 150Sn/80 kVp to -4.0% (IQR -6.0, -2.8%) at 150Sn/90 kVp. For DLCT, median measurement errors ranged from -3.3% (IQR -4.9, -1.5%) at 140 kVp to -4.6% (IQR -6.0, -3.6%) at 120 kVp. Larger phantom sizes increased variability of iodine measurements (p < 0.05). CONCLUSION: Iodine concentration can be accurately quantified with state-of-the-art DECT systems from two vendors. The lowest absolute errors were found for DSCT using the 150Sn/70 kVp or 150Sn/80 kVp combinations, which was slightly more accurate than 140 kVp in DLCT. KEY POINTS: • High-end CT scanners allow accurate iodine quantification using different DECT techniques. • Lowest measurement error was found in scans with largest photon energy separation. • Dual-source CT quantified iodine slightly more accurately than dual layer CT.

Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography.

Contrast-enhanced micro-computed tomography (CEµCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEµCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEµCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEµCT method for 3D characterization of articular cartilage.

Contrast-enhanced CT imaging as a non-destructive tool for ex vivo examination of the biochemical content and structure of the human meniscus.

The biochemical and histopathological techniques used to investigate meniscal content and structure are destructive and time-consuming. Therefore, this study evaluated whether contrast-enhanced computed tomography (CECT) attenuation and contrast agent flux using the iodinated contrast agents CA4+ and ioxaglate correlate with the glycosaminoglycan (GAG) content/distribution and water content in human menisci. The optimal ioxaglate and CA4+ contrast agent concentrations for mapping meniscal GAG distribution were qualitatively determined by comparison of CECT color maps with Safranin-O stained histological sections. The associations between CECT attenuation and GAG content, CECT attenuation and water content, and flux and water content at various time points were determined using both contrast agents. Depth-wise analyses were also performed through each of the native surfaces to examine differences in contrast agent diffusion kinetics and equilibrium partitioning. The optimal concentrations for GAG depiction for ioxaglate and CA4+ were ≥80 and 12 mgI/ml, respectively. Using these concentrations, weak to moderate associations were found between ioxaglate attenuation and GAG content at all diffusion time points (1-48 h), while strong and significant associations were observed between CA4+ attenuation and GAG content as early as 7 h (R2 ≥ 0.67), being strongest at the equilibrium time point (48 h, R2 = 0.81). CECT attenuation for both agents did not significantly correlate with water content, but CA4+ flux correlated with water content (R2 = 0.56-0.64). CECT is a promising, non-destructive imaging technique for ex vivo assessment of meniscal GAG concentration and water content compared to traditional biochemical and histopathological methods. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1018-1028, 2017.

Contrast-enhanced µCT of the intervertebral disc: A comparison of anionic and cationic contrast agents for biochemical and morphological characterization.

The objective of this study was to quantify and compare the contrast-enhancing properties of the anionic contrast agent ioxaglate/Hexabrix, and cationic contrast agent CA4+ for biochemical and morphological characterization of the intervertebral disc (IVD) via µCT. Optimal contrast agent concentrations were determined by incubating rat lumbar IVDs in dilutions of Hexabrix-320 (20%, 30%, 40%, and 50%) and CA4+ (10, 20, 30, and 40 mg I/ml). µCT imaging was performed at 70 kVp, 114 µA, and 250 ms integration time, 12 µm voxel size. The kinetics of contrast enhancement were quantified with cumulative incubations for 0.5, 1, 2, 12, 16, 20, and 24 h using both agents. Agreement in morphological quantification was assessed via serial scans of the same IVDs. Correlation of attenuation to glycosaminoglycan (GAG) content was determined by enzymatic digestion of IVDs, subsequent µCT imaging, and GAG quantification via dimethylmethylene blue assay. Forty percent Hexabrix and 30 mg I/ml CA4+ were chosen as optimal concentrations. Hexabrix enabled greater delineation of the IVD from surrounding tissues, and CA4+ had the lowest uptake in surrounding soft tissue. Twenty-four hour incubation was sufficient for >99% equilibration of both agents. A high level of agreement was observed in the quantification of IVD volume (ICC = 0.951, r = 0.997) and height (ICC = 0.947, r = 0.991). Both agents exhibited strong linear correlations between µCT attenuation and GAG content (Hexabrix: r = -0.940; CA4+ : r = 0.887). Both agents enable biochemical and morphological quantification of the IVD via contrast-enhanced µCT and are effective tools for preclinical characterization. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1067-1075, 2017.

Severe thrombocytopenia induced by iodinated contrast after coronary angiography: The use of gadolinium contrast and intravascular ultrasound as an alternative to guide percutaneous coronary intervention.

Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. His platelet count after the procedure with the highest amount of contrast was zero, which is the lowest reported platelet count to date. Percutaneous coronary revascularization under both intravascular ultrasound and gadolinium contrast guidance was performed without complications. The most feared complication after the use of gadolinium is nephrogenic systemic fibrosis, especially in patients on hemodialysis.

Three-dimensional cone-beam CT sialography in non tumour salivary pathologies: procedure and results.

OBJECTIVES: Non-tumour salivary diseases are common. Imaging studies are essential for their diagnosis and before undergoing an endoscopic or surgical treatment. In this study, we aimed at presenting our procedure and results obtained with three-dimensional CBCT (3D-CBCT) sialography for non-tumour salivary gland diseases. METHODS: Patients with parotid or submandibular salivary symptoms were examined by 3D-CBCT sialography. They received an intraductal injection of 0.5 mL of water-soluble contrast medium maintained in the gland, followed by examination in a NewTom wide-field CBCT device. Images were processed with multiplanar and 3D reconstructions. RESULTS: A ductal exploration could be performed until the fourth divisions. The main lesions found were stones, stenosis, dilatations and "dead tree" appearance of the ductal system. No side effects of the catheterization or the iodine contrast were reported, nor tissue damages related to the contrast keeping technique. CONCLUSIONS: 3D-CBCT sialography seems to represent a reliable non-invasive diagnostic tool for ductal salivary diseases. More studies are needed to assess the value of 3D-CBCT sialography compared with conventional imaging.

Quantitative Evaluation of the Mechanical Risks Caused by Focal Cartilage Defects in the Knee.

Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains. Both strain values experienced up to 3-fold increase, exceeding levels previously associated with chondrocyte apoptosis and failure of collagen crosslinks. Furthermore, defects at the central regions of medial tibial cartilage with direct cartilage-cartilage contact were the most vulnerable to loading. Also locations under the meniscus experienced substantially increased minimum principal strains. We suggest that during knee joint loading particularly minimum principal and shear strains are increased above tissue failure limits around cartilage defects which might lead to osteoarthritis. However, this increase in strains is highly location-specific on the joint surface.