Noninvasive monitoring of chick development in ovo using a 7T MRI system from day 12 of incubation through to hatching

PURPOSE: To determine whether mild cooling of the egg reduces movement to the point where an ultra-high-field (7T) MRI system can be used to noninvasively monitor chick growth in ovo from 12 days incubation through to hatching. MATERIALS AND METHODS: Group A eggs were incubated at 37.5 degrees C for 21 days. Group B eggs were removed from the incubator on days 12, 15, 17, 18, 19, and 20 of incubation, cooled for one hour, and then returned to the incubator. Group C eggs were cooled as for group B and then individually imaged for 25 minutes using a 7T MRI system before being returned to the incubator. The average size (volume) of the heart, liver, and brain at each stage of incubation was estimated from the T2-weighted images and compared with existing values in the literature. RESULTS: The combination of cooling and MRI significantly reduced chick movement to allow excellent image acquisition at each stage of incubation. Repeated cooling and/or MRI did not significantly slow down or arrest the development of the chicks in either of the experimental groups. CONCLUSION: MRI provides a powerful noninvasive tool to study chick development and the growth of individual organs, including the brain, liver, and heart, in ovo from 12 days' incubation.     

T1 assessment of hip joint cartilage following intra‐articular gadolinium injection: A pilot study

This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra‐articular delayed gadolinium‐enhanced MRI of cartilage (ia‐dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty‐seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra‐articular delayed gadolinium‐enhanced MRI of cartilage. These T₁ findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre‐ and postcontrast T₁ values (P < 0.001) remaining constant for 45 min. We noted higher mean T₁ values in morphologically normal‐appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior‐superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra‐articular delayed gadolinium‐enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Strain‐dependent T1 relaxation profiles in articular cartilage by MRI at microscopic resolutions

To investigate the dependency of T₁ relaxation on mechanical strain in articular cartilage, quantitative magnetic resonance T₁ imaging experiments were carried out on cartilage before/after the tissue was immersed in gadolinium contrast agent and when the tissue was being compressed (up to ～48% strains). The spatial resolution across the cartilage depth was 17.6 μm. The T₁ profile in native tissue (without the presence of gadolinium ions) was strongly strain‐dependent, which is also depth‐dependent. At the modest strains (e.g., 14% strain), T₁ reduced by up to 68% in the most surface portion of the tissue. Further compression (e.g., 45% strain) reduced T₁ mostly in the middle and deep portions of the tissue. For the gadolinium‐immersed tissue, both modest and heavy compressions (up to 48% strain) increased T₁ slightly but significantly, although the overall shapes of the T₁ profiles remained approximately the same regardless of the amount of strains. The complex relationships between the T₁ profiles and the mechanical strains were a direct consequence of the depth‐dependent proteoglycan concentration in the tissue, which determined the tissue's mechanical properties. This finding has potential implications in the use of gadolinium contrast agent in clinical magnetic resonance imaging of cartilage (the dGEMRIC procedure), when the loading or loading history of patients is considered. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Feasibility of in ovo diffusion tractography in the chick embryo using a dual-cooling technique

Purpose:

To evaluate the capability of a dual‐cooling technique in suppressing motion artifact and to evaluate the feasibility of the noninvasive muscle fibers tracking using DTI during chick embryonic development.

Materials and Methods:

Fifteen eggs were divided into three groups of 5 eggs each (one group for each imaging sequence), and eggs were imaged every 48 h from incubation day 4; embryos were imaged in ovo using three sequences of varying duration (T1, T2, and DTI). For each sequence, three preprocessing methods were used: no‐cooling (NC), single‐cooling (SC), and dual‐cooling (DC). Two independent observers assessed images for motion artifact. The results of different preprocessing methods used for each sequence were compared by the χ² test. The Cohen kappa test was used to assess the interobserver variability.

Results:

For T1 imaging, motion artifact was adequately suppressed by both SC and DC methods (χ² test; P > 0.05). For T2 imaging, motion artifact was also sufficiently suppressed by both SC and DC methods (χ² test; P > 0.05) except incubation day 19 (χ² test; P < 0.001). For DTI, motion artifact was less with DC than SC after 8 days (χ² test; P < 0.05). Hindlimb muscle fibers of chick embryo could be serially evaluated with DTI from 8 days using dual‐cooling technique.

Conclusion:

The dual‐cooling technique enables DTI of chick embryo in ovo with minimal motion artifact, which permits muscle fiber tracking by DTI during chick embryonic development possible, and can improve the imaging quality of conventional MRI with long duration and those sensitive to motion. J. Magn. Reson. Imaging 2012;36:993–1001. © 2012 Wiley Periodicals, Inc.     

Three-dimensional delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) for in vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3.0T: Preliminary results

PURPOSE: To use a 3D gradient-echo (GRE) sequence with two flip angles for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to evaluate relative glycosaminoglycan content of repair tissue after matrix-associated autologous chondrocyte transplantation (MACT). MATERIALS AND METHODS: In a phantom study, T1-mapping based on a 3D-GRE sequence with different flip angle combinations was compared with a standard inversion recovery (IR) sequence at 3.0T. Fifteen patients were examined after MACT in the knee at "3-13 months" (group I) and "19-42 months" (group II). The delta relaxation rate (deltaR1) calculated for repair tissue and normal hyaline cartilage was measured and mean values were compared in different postoperative intervals using analysis of variance. RESULTS: The flip angle combination 35/10 degrees provided the best agreement with IR sequence for short and long T1 values. The mean deltaR1 for repair tissue was 2.49 versus 1.04 at the intact control site in group I and 1.90 compared with 0.81 in group II. Differences from repair tissue to control sites showed statistically significance for both groups; no significant difference was found between groups. CONCLUSION: The 3D dual flip angle dGEMRIC technique optimized for cartilage imaging is comparable to standard T1 IR technique for T1 mapping. Furthermore, the preliminary in vivo study demonstrates the feasibility of the technique in the evaluation of MACT patients.     

In vivo MRI of fresh stored osteochondral allograft transplantation with delayed gadolinium‐enhanced MRI of cartilage: Protocol considerations and recommendations

The protocol for delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) was adapted for the evaluation of transplanted osteochondral allograft cartilage. Eight patients with focal grade 4 cartilage defects of the femoral condyle were treated with single cylindrical osteochondral allografts. At 1 and 2 years, dGEMRIC image sequences were acquired and regions of interest (ROIs) were drawn in repair and native control cartilage. Mean T₁ values of region of interest were used to calculate established dGEMRIC metrics. The correlation was measured between the ΔR₁ and R₁‐Post metrics for repair and native cartilage. T₁ times were measured in deep and superficial zones of cartilage. A strong correlation was identified between full‐thickness, deep, and superficial ΔR₁ and R₁‐Post values for native cartilage and repair cartilage for all years (range: 0.893–1.0). The mean T₁ times and ΔR₁ rate between deep and superficial regions of articular cartilage were statistically different for all regions of the distal femora analyzed at 1 year and 2 years after osteochondral allograft transplantation (P < 0.05). The dGEMRIC pre‐Gadolinium scan is unnecessary when evaluating transplanted osteochondral allograft cartilage. The observation of stratified T₁ and ΔR₁ values indicates a need to re‐evaluate the methodology behind the placement of region of interest in dGEMRIC. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Feasibility of T mapping for the evaluation of hip joint cartilage at 1.5T using a three‐dimensional (3D), gradient‐echo (GRE) sequence: A prospective study

This study defines the feasibility of utilizing three‐dimensional (3D) gradient‐echo (GRE) MRI at 1.5T for T mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T mapping without gadolinium‐enhancement utilizing a 3D‐GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual‐flip‐angle 3D‐GRE sequence for dGEMRIC T₁ mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T₁ and T findings were subsequently correlated. There were significant differences between volunteers and patients in normally‐rated cartilage only for T₁ values. Both T₁ and T values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T (T₁) (P < 0.05). High intraclass correlation was noted for both T₁ and T. Correlation factor was 0.860 to 0.954 (T‐T₁ intraobserver) and 0.826 to 0.867 (T‐T₁ interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T mapping at 1.5T. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Variable flip angle‐based fast three‐dimensional T1 mapping for delayed gadolinium‐enhanced MRI of cartilage of the knee: Need for B1 correction

Delayed gadolinium‐enhanced MRI of cartilage is a technique, which involves T₁ mapping to identify changes in the structural integrity of cartilage associated with osteoarthritis. Currently, the gold standard is 2D inversion recovery turbo spin echo, which suffers from long acquisition times and limited coverage. Three‐dimensional variable flip angle (VFA) is an alternate technique, which has been shown to be accurate when an estimate of T₁ is available a priori. This study validates the variable flip angle method for delayed gadolinium‐enhanced MRI of cartilage of the femoro‐tibial knee cartilage. When amplitude of (excitation) radiofrequency field inhomogeneities were minimized using nonselective pulses and amplitude of (excitation) radiofrequency field correction using an additional acquisition of a amplitude of (excitation) radiofrequency field map, the accuracy of T₁ measurements were improved, and slice‐to‐slice variations over the 3D volume were minimized. In conclusion, fast 3D T₁ mapping using the variable flip angle method with amplitude of (excitation) radiofrequency field correction appears to be an efficient and accurate method for delayed gadolinium‐enhanced MRI of cartilage of the knee. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

The impact of the relaxivity definition on the quantitative measurement of glycosaminoglycans in cartilage by the MRI dGEMRIC method

The relaxivities (R‐values) of the gadolinium diethylene triamine pentaacetic acid (Gd(DTPA)^2?) ions in a series of skim‐milk solutions at 0–40% milk concentrations were measured using NMR spectroscopy. The R‐value was found to be approximately linearly proportional to the concentration of the solid component in the milk solution. Using the R‐value at 20% solid component (approximately the solid concentration in bovine nasal cartilage), the glycosaminoglycan concentration in bovine nasal cartilage can be quantified using the MRI delayed gadolinium‐enhanced MRI of cartilage method without the customary scaling factor of 2. This finding is also supported by the measurements using ²³Na NMR spectroscopy, ²³Na inductively coupled plasma analysis, and biochemical assay. The choice of the R‐value definition in the MRI delayed gadolinium‐enhanced MRI of cartilage method is discussed, and the definition of Gd(DTPA)^2? ions as “millimole per volume of tissue (or milk solution for substitution)” should be used. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Three‐dimensional micro‐MRI analysis of cerebral artery development in mouse embryos

Vascular system development involves a complex, three‐dimensional branching process that is critical for normal embryogenesis. In the brain, the arterial systems appear to develop in a stereotyped fashion, but no detailed quantitative analyses of the mouse embryonic cerebral arteries have been described. In this study, a gadolinium‐based contrast perfusion method was developed to selectively enhance the cerebral arteries in fixed mouse embryos. Three‐dimensional magnetic resonance micro‐imaging (micro‐MRI) data were acquired simultaneously from multiple embryos staged between 10 and 17 days of gestation, and a variety of image analysis methods was used to extract and analyze the cerebral arterial patterns. The results show that the primary arterial branches in the mouse brain are very similar between individuals, with the patterns established early and growth occurring by extension of the segments, while maintaining the underlying vascular geometry. To investigate the utility of this method for mutant mouse phenotype analysis, contrast‐enhanced micro‐MRI data were acquired from Gli2^‐/‐ mutant embryos and their wild‐type littermates, showing several previously unreported vascular phenotypes in Gli2^?/? embryos, including the complete absence of the basilar artery. These results demonstrate that contrast‐enhanced micro‐MRI provides a powerful tool for analyzing vascular phenotypes in a variety of genetically engineered mice. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Delayed gadolinium‐enhanced MRI of cartilage in the ankle at 3 T: Feasibility and preliminary results after matrix‐associated autologous chondrocyte implantation

Purpose:

To demonstrate the feasibility of delayed gadolinium‐enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the ankle at 3 T and to obtain preliminary data on matrix associated autologous chondrocyte (MACI) repair tissue.

Materials and Methods:

A 3D dual flip angle sequence was used with an eight‐channel multipurpose coil at 3 T to obtain T1 maps both pre‐ and postintravenous contrast agent (Magnevist, 0.2 mM/kg). Postcontrast T1 over time was evaluated in three volunteers; a modified dGEMRIC protocol was then used to assess 10 cases after MACI in the ankle.

Results:

Forty‐five minutes were found sufficient for maximum T1 decrease. MACI cases had a precontrast mean T1 of 1050 ± 148.4 msec in reference cartilage (RC) and 1080 ± 165.6 msec in repair tissue (RT). Postcontrast T1 decreased to 590 ± 134.0 msec in RC and 554 ± 133.0 msec in RT. There was no significant difference between the delta relaxation rates in RT (9.44 × 10^?4 s^?1) and RC (8.04 × 10^?4 s^?1, P = 0.487). The mean relative delta relaxation rate was 1.34 ± 0.83.

Conclusion:

It is feasible to assess the thin cartilage layers of the ankle with dGEMRIC at 3 T; MACI can yield RT with properties similar to articular cartilage. J. Magn. Reson. Imaging 2010;31:732–739. © 2010 Wiley‐Liss, Inc.

     

Quantitative cartilage volume measurement using MRI: comparison of different evaluation techniques

This study was aimed to investigate the accuracy and time saving of MRI Argus application in the assessment of cartilage volume in osteoarthritic knees. Twelve knees of patients suffering from osteoarthritis were scanned with a 1.5 T MRI using a 3D gradient echo sequence with selective water excitation. Cartilage volume of the tibial and patellar compartment was determined with a validated multiprocessing computer system (Octane Duo, Silicon Graphics, Mountain View, Calif., USA). The calculated cartilage volumes were compared to the results acquired by the Argus (Siemens Inc., Erlangen, Germany) application software using the MRI data sets. Compared to the multiprocessing computer system a time saving of at least 30 min for cartilage volume determination was achieved. The mean differences of Argus versus the multiprocessing computer system were 4.26±0.84 and 7.80±0.87% for the medial and lateral tibial plateau and 5.94±0.59% for the patella (no statistical significant difference; P>0.05). The applied Argus software can be used for fast and accurate determination of cartilage volume in the knee joint.The authors certify that there is no actual or potential conflict of interest in relation to this article     

Further studies on the anisotropic distribution of collagen in articular cartilage by μMRI

To further study the anisotropic distribution of the collagen matrix in articular cartilage, microscopic magnetic resonance imaging experiments were carried out on articular cartilages from the central load‐bearing area of three canine humeral heads at 13 μm resolution across the depth of tissue. Quantitative T₂ images were acquired when the tissue blocks were rotated, relative to B₀, along two orthogonal directions, both perpendicular to the normal axis of the articular surface. The T₂ relaxation rate (R₂) was modeled, by three fibril structural configurations (solid cone, funnel, and fan), to represent the anisotropy of the collagen fibrils in cartilage from the articular surface to the cartilage/bone interface. A set of complex and depth‐dependent characteristics of collagen distribution was found in articular cartilage. In particular, there were two anisotropic components in the superficial zone and an asymmetrical component in the radial zone of cartilage. A complex model of the three‐dimensional fibril architecture in articular cartilage is proposed, which has a leaf‐like or layer‐like structure in the radial zone, arises in a radial manner from the subchondral bone, spreads and arches passing the isotropic transitional zone, and exhibits two distinct anisotropic components (vertical and transverse) in the surface portion of the tissue. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

In vivo measurement of gadolinium diffusivity by dynamic contrast‐enhanced MRI: A preclinical study of human xenografts

Compartmental tracer kinetic models currently used for analysis of dynamic contrast‐enhanced MRI data yield poor fittings or parameter values that are unphysiological in necrotic regions of the tumor, as these models only describe microcirculation in perfused tissue. In this study, we explore the use of Fick's law of diffusion as an alternative method for analysis of dynamic contrast‐enhanced MRI data in the necrotic regions. Xenografts of various human cancer cell lines were implanted in 14 mice that were subjected to dynamic contrast‐enhanced MRI performed using a spoiled gradient recalled sequence. Tracer concentration was estimated using the variable flip angle technique. Poorly perfused and necrotic tumor regions exhibiting delayed and slow enhancement were identified using a k‐means clustering algorithm. Tracer behavior in necrotic regions was shown to be consistent with Fick's diffusion equation and the in vivo gadolinium diffusivity was estimated to be 2.08 (±0.88) × 10^?4 mm²/s. This study proposes the use of gadolinium diffusivity as an alternative parameter for quantifying tracer transport within necrotic tumor regions. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Decreased incidence of NSF in patients on dialysis after changing gadolinium contrast‐enhanced MRI protocols

Purpose:

To retrospectively determine the incidence of nephrogenic systemic fibrosis (NSF) in patients on dialysis administered either a lower dose high‐relaxivity linear gadolinium‐chelate, gadobenate dimeglumine (MultiHance, MH), compared to a standard dose linear gadolinium chelate, gadodiamide (Omniscan, OM).

Materials and Methods:

This study was Health Insurance Portability and Accountability Act (HIPAA)‐compliant and Institutional Review Board (IRB)‐approved. As per institution standardized contrast‐enhanced magnetic resonance imaging (MRI) protocols, patients on dialysis were imaged using either MH, between 2/2007 to 9/2008, or OM between 10/2003 and 1/2007. Rates of NSF were compared using 95% score‐based confidence intervals (CI). The Wilcoxon rank sum test was used to test similarity/difference between contrast doses given to each patient group.

Results:

Overall, 312 patients on dialysis received OM and eight (2.6%) developed NSF (95% CI: 1.30%–4.98%). In all, 784 patients on dialysis received MH at a mean cumulative dose of 0.11 mmol/kg (0.05–0.75 mmol/kg) and no cases of NSF were identified (upper 95% confidence bound of 0.45%). The mean cumulative dose of OM was 0.16 mmol/kg (0.1–0.9 mmol/kg) for all patients and 0.28 mmol/kg (0.1–0.8 mmol/kg) for the patients with NSF. The median OM dose was greater in patients who developed NSF (P = 0.03), and was greater than the median MH dose (P < 0.005).

Conclusion:

NSF incidence in at‐risk patients receiving contrast‐enhanced MRI can be reduced after changing contrast administration protocols that includes changing the type and dose of contrast agent. J. Magn. Reson. Imaging 2010; 31: 440–446. © 2010 Wiley‐Liss, Inc.     

Quantitative evaluation of oxygenation in venous vessels using T2‐Relaxation‐Under‐Spin‐Tagging MRI

Noninvasive measurement of cerebral venous oxygenation can serve as a tool for better understanding fMRI signals and for clinical evaluation of brain oxygen homeostasis. In this study a novel technique, T2‐Relaxation‐Under‐Spin‐Tagging (TRUST) MRI, is developed to estimate oxygenation in venous vessels. This method uses the spin labeling principle to automatically isolate pure blood signals from which T2 relaxation times are determined using flow‐insensitive T2‐preparation pulses. The blood T2 is then converted to blood oxygenation using a calibration plot. In vivo experiments gave a baseline venous oxygenation of 64.8 ± 6.3% in sagittal sinus in healthy volunteers (n = 24). Reproducibility studies demonstrated that the standard deviation across trials was 2.0 ± 1.1%. The effects of repetition time and inversion time selections were investigated. The TRUST technique was further tested using various physiologic challenges. Hypercapnia induced an increase in venous oxygenation by 13.8 ± 1.1%. On the other hand, caffeine ingestion resulted in a decrease in oxygenation by 7.0 ± 1.8%. Contrast agent infusion (Gd‐DTPA, 0.1 mmol/kg) reduced venous blood T2 by 11.2 ms. The results of this study show that TRUST MRI is a useful technique for quantitative assessment of blood oxygenation in the brain. Magn Reson Med 60:357–363, 2008. © 2008 Wiley‐Liss, Inc.