Hip dGEMRIC in asymptomatic volunteers and patients with early osteoarthritis: the influence of timing after contrast injection.

Eight asymptomatic volunteers and 10 patients with early hip osteoarthritis (OA) were investigated with hip delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 30, 65, 100, and 135 min after IV injection with Gd-DTPA(2-). In asymptomatic volunteers there was a decrease in the dGEMRIC index (T(1)(Gd)) between 30 and 100 min. In patients the wash-in of Gd-DTPA(2-) was faster, with a low T(1)(Gd) at 30 min that did not change significantly over time. Therefore, earlier time points showed a larger separation in T(1)(Gd) between asymptomatic and OA hips, with more convenient timing logistics. However, T(1)(Gd) at 30 min had a larger standard deviation (SD) in the OA group, possibly due to variability of the steep slope of wash-in. This sensitivity to the imaging window may be less desirable for longitudinal studies in which reproducibility is a concern. At all time points, T(1)(Gd) was 20-30% lower in patients than in asymptomatic volunteers (P < 0.003), which demonstrates the sensitivity of dGEMRIC to early hip OA.     

Delayed contrast‐enhanced MRI of cartilage: Comparison of nonionic and ionic contrast agents

The objective of this study was to evaluate if cartilage fixed charge density is the only factor determining the distribution of the measured delayed gadolinium‐enhanced magnetic resonance imaging of cartilage index, T₁(Gd‐DTPA^2?), across cartilage in the clinical delayed gadolinium‐enhanced magnetic resonance imaging of cartilage protocol. Nineteen subjects with osteoarthritis and 14 controls were included. Cartilage T₁(Gd) was measured following administration of 0.2 mmol kg^?1 of nonionic (Gd‐DTPA‐BMA) and, at a different date, anionic (Gd‐DTPA^2?). T₁(Gd‐DTPA‐BMA) was plotted against T₁(Gd‐DTPA^2?); a slope of 0 would indicate domination by charge effects; a nonzero slope would suggest that other factors influence T₁(Gd‐DTPA‐BMA), and hence potentially T₁(Gd‐DTPA^2?). The low slope of the curve found in osteoarthritis subjects (0.31) indicates that Gd‐DTPA‐BMA penetrated most osteoarthritis cartilage to the same extent, and T₁(Gd‐DTPA‐BMA) did not differentiate cartilages, which were differentiated by T₁(Gd‐DTPA^2?). The higher slopes in control subjects (0.88) are possibly due to inhibited transport of contrast agent into healthier cartilage, potentially exaggerated by the fast body clearance of the nonionic contrast agent. Overall, the use of anionic Gd‐DTPA^2? for delayed gadolinium‐enhanced magnetic resonance imaging of cartilage is indicated for better discrimination of the health status of cartilage. Future studies could be designed to use contrast‐enhanced dynamics to understand the transport properties of tissues in the joint and to evaluate the concentration of tissue constituents. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo assessment of macromolecular content in articular cartilage of the goat knee.

Loss of proteoglycans (PGs) from the extracellular matrix of cartilage is an early event of osteoarthritis. The capability of Gd(DTPA)(2-)-enhanced MRI to quantitatively assess PG content was explored in a goat model of cartilage degeneration. Partial to total PG depletion was induced by an intraarticular injection of papain 1 day prior to the MRI session. A close correlation was found between the extent of the PG loss and the Gd(DTPA)(2-)-induced T(1) decrease. Papain-induced PG depletion was confirmed by post-mortem histological and biochemical assessments. A 2-hr delay after Gd(DTPA)(2-) injection was found to be optimal for an accurate quantitation of the cartilage defect. A series of knee flexions were performed post-Gd(DTPA)(2-) injection to facilitate penetration of the contrast agent into cartilage. However, DeltaT(1)'s observed in cartilage of exercised goat knees were not affected by papain or IL1beta pretreatment. Therefore, as long as a preinjection T(1) map was obtained, the Gd(DTPA)(2-)-enhanced MRI technique provided good sensitivity in detecting partial loss of PG in articular cartilage. This was true only when the animal was maintained in a resting state during diffusion of the Gd(DTPA)(2-). This approach is of particular interest for long-term evaluations of cartilage degeneration and regeneration.     

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.     

Quantitative imaging of cartilage morphology at 3.0 Tesla in the presence of gadopentate dimeglumine (Gd-DTPA).

MRI-based cartilage morphometry was previously validated in the absence of gadopentate dimeglumine (Gd-DTPA). However, Gd-DTPA is required for compositional (proteoglycan) imaging using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Therefore, the effect of Gd-DTPA on cartilage morphometry was studied. A total of 165 female participants (67 with and 98 without osteoarthritis [OA]) were imaged at 3.0 Tesla before and 2 hr after intravenous Gd-DTPA injection. Flip angles in post-Gd-DTPA scans varied between 12 degrees and 35 degrees . Cartilage volume and thickness of post- vs. pre-Gd-DTPA scans showed intraclass correlation coefficients (ICCs) of 0.85 > or = r > or = 0.95, mean differences between -2.1% and +1.1%, and standard deviations (SDs) of differences between 4.7% and 9.2%. Mixed-effect models found no consistent impact of flip angle and OA status on post- vs. pre-Gd-DTPA differences. Accurate morphological measurements of cartilage can be obtained after Gd-DTPA injection, allowing compositional and morphological imaging to be combined into one session.     

In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis

Objective To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).Design Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k _m for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network. Local changes in cartilage fixed charge density, i.e., where PGs are depleted, were derived from T₁ relaxation maps as obtained after an infusion of Gd(DTPA)²⁻, a paramagnetic agent.Results In the goat model, the MT rate constant k _m was significantly higher at 2 weeks post surgery, a possible sign of cartilage swelling, then decreased below baseline values, most likely indicative of disruption in the collagen framework. Meanwhile, post-Gd(DTPA)²⁻ MRI acquisition indicated a significant and sustained loss of PGs. The rabbit model produced milder lesions. Although the difference was non-significant, k _m steadily decreased in response to the surgical insult while kinetics of Gd(DTPA)²⁻ uptake, after reaching a peak level at 6 weeks, were back to normal values after 12 weeks.Conclusion In the goat model, joint instability and cartilage damage was a permanent trigger for cartilage degeneration producing MRI changes. However, biomechanical stress due to partial medial meniscectomy in knees of mature rabbits produced only mild, focal lesions and PG depletion that was partially reversible. This proof-of-concept study identified MT and T₁ parameters as useful surrogate markers in animal models of osteoarthritis.     

Suitability of T(1Gd) as the dGEMRIC index at 1.5T and 3.0T.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is based on the theory that Gd-DTPA(2-) will distribute in inverse relation to cartilage glycosaminoglycan (GAG). T(1Gd) (T(1) after penetration of a 0.2 mmol/kg dose of Gd-DTPA(2-)) has been used as the dGEMRIC index, although (1/T(1Gd)-1/T(1o)) should be more representative of Gd-DTPA(2-) concentration (where T(1o) = T(1) before contrast). T(1o) and T(1Gd) were measured in 20 volunteers at both 1.5T and 3T and the correlation between the metrics of T(1Gd) and (1/T(1Gd)-1/T(1o)) was calculated. There was a high correlation coefficient between the two metrics at both field strengths, with R = 0.94, 0.93, and 0.90 for central medial femur, posterior medial femur, and medial tibia, respectively, at 1.5T and 0.87, 0.94, 0.96 at 3T. In all cases P < 0.0001. Therefore, these data suggest that, for native cartilage, the current practice of measuring T(1Gd) (but not also T(1o)) is adequate at both 1.5T and 3T.     

Investigation using an HER‐2/neu transgenic mouse model of a newly developed MR contrast agent with the effect of an antitumor drug

Purpose

To assess whether Gd‐DTPA‐Gel‐Cis, a conjugate of gadolinium (Gd), cis diamminedichloroplatinum (Cis), diethylenetriaminepentaacetic acid (DTPA)‐dianhydride, and bovine gelatin (Gel) can be used as an intravascular contrast agent at MRI and as an antitumor cell proliferation agent in vitro.

Materials and Methods

We injected Gd‐DTPA‐Gel‐Cis (200 mg/mL) into the caudal vein of female HER‐2/neu transgenic mice with spontaneous mammary tumors. The tumor signal intensity was measured with a 0.3 Tesla MRI scanner. HER‐2/neu‐expressing NT cells were treated with Gd‐DTPA‐Gel‐Cis (5 μM cisplatin, 200 mg/mL Gel), Cis alone (5 μM cisplatin), or Gel alone (200 mg/mL gelatin). Differences of P < 0.05 were considered to be statistically significant.

Results

On T1‐weighted MRI scans of mice injected with Gd‐DTPA‐Gel‐Cis we observed a 23% increase in signal intensity. The survival rates of cells exposed to Gd‐DTPA‐Gel‐Cis or Cis were 70.9% and 58.3%, respectively, of the survival rates observed after treatment with Gel alone. Gd‐DTPA‐Gel‐Cis showed significant toxicity (P < 0.05).

Conclusion

Gd‐DTPA‐Gel‐Cis shows promise for use as an MRI contrast medium and as an antitumor agent. J. Magn. Reson. Imaging 2009;30:907–910. © 2009 Wiley‐Liss, Inc.     

In vivo transport of Gd-DTPA(2-) in human knee cartilage assessed by depth-wise dGEMRIC analysis

Purpose:

To investigate the transport of Gd‐DTPA^2? in different layers of femoral knee cartilage in vivo.

Materials and Methods:

T₁ measurements (1.5 Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The weight‐bearing central cartilage was analyzed before contrast and at eight time points after an intravenous injection of Gd‐DTPA^2?: 12–60 min (4 volunteers) and 1–4 h (19 volunteers). Three regions of interest were segmented manually: deep, middle, and superficial.

Results:

Before contrast injection, a depth‐wise variation of T₁ was observed with 50% higher values in the superficial region compared with the deep region. In the deep region, the uptake of Gd‐DTPA^2? was not detected until 36 min and the concentration increased until 240 min, whereas in the superficial region, the uptake was seen already at 12 min and the concentration decreased after 180 min (P < 0.01). There was a difference between medial and lateral compartment regarding bulk, but not superficial Gd‐DTPA^2? concentration. The bulk gadolinium concentration was negatively related to the cartilage thickness (r = ?0.68; P < 0.01).

Conclusion:

The depth‐wise and thickness dependent variations in Gd‐DTPA² transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd‐DTPA² will yield a falsely too long T₁. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

     

Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI)

Purpose

To elucidate whether a contrast agent dilution method (dilution method), in which gadoxetate disodium (Gd‐EOB‐DTPA) is diluted with saline, is useful for good‐quality arterial‐phase images.

Materials and Methods

In this study we observed 494 hypervascular hepatocellular carcinomas (HCCs) in 327 patients with chronic liver disease. Three Gd‐EOB‐DTPA injection methods were adopted for comparison: 1) test injection method (undiluted Gd‐EOB‐DTPA and modified scan delay), in which a test dose of 0.5 mL of Gd‐EOB‐DTPA was injected to determine scan delay; 2) conventional method (undiluted Gd‐EOB‐DTPA and fixed scan delay); and ( 3 ) dilution method (diluted Gd‐EOB‐DTPA and fixed scan delay), in which Gd‐EOB‐DTPA was diluted to 20 mL with saline. Lesion‐liver contrast was calculated. Image quality and lesion detectability were evaluated by two radiologists blinded to the injection methods.

Results

The lesion‐liver contrast of the dilution method was significantly higher than that of the other two methods. Lesion detectability of the conventional method (64%) was significantly lower than that of the other two methods (contrast agent dilution method, 95%; test injection method, 93%). The image quality of the contrast agent dilution method was significantly better than that of the other two methods.

Conclusion

The dilution method contributed to improved image quality, high lesion‐liver contrast, and high lesion detectability in the arterial‐phase images of GD‐EOB‐DTPA‐enhanced MRI. J. Magn. Reson. Imaging 2009;30:849–854. © 2009 Wiley‐Liss, Inc.     

Effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of Gd-EOB-DTPA: evaluation using MRI of conscious mice

Purpose:

To develop a method for body magnetic resonance imaging (MRI) of conscious mice and investigate the effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of gadoxetate disodium (Gd‐EOB‐DTPA).

Materials and Methods:

Conscious or anesthetized mice were restrained on a holder and the rectal temperature was measured serially. Serial MRI of the liver was performed after intravenous injection of Gd‐EOB‐DTPA with or without temperature control. Three mice were studied for each condition.

Results:

The temperature dropped rapidly in anesthetized mice beside the MR unit. The decline was less prominent in conscious mice. The temperature decreased less in anesthetized mice and remained constant in conscious mice in the radiofrequency (RF) coil. The washout of Gd‐EOB‐DTPA was slower in anesthetized hypothermic mice than in conscious normothermic mice. Warmed anesthetized mice showed faster washout, and cooled conscious mice showed delayed washout. Severer hypothermia in anesthetized mice resulted in weaker initial enhancement and slower washout.

Conclusion:

By separately manipulating the presence or absence of anesthesia and hypothermia, we demonstrated that washout of Gd‐EOB‐DTPA was delayed under hypothermia, regardless of anesthesia. Serial body MRI of conscious mice was feasible and allowed the evaluation of kinetics of a contrast agent, while excluding the possible effects of anesthesia. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Relaxivity and diffusion of gadolinium agents in cartilage.

Prior work indicates that the distribution of Gd(DTPA)(2-) (as measured by T(1)) is a good surrogate measure of the distribution of gycosaminoglycan (GAG) in cartilage. In addition to the measured T(1) in the presence of Gd(DTPA)(2-), the precision of the measurement of Gd(DTPA)(2-) concentration depends on the T(1) without Gd(DTPA)(2-) (T(o)(1)), and the relaxivity (r) of Gd(DTPA)(2-) in cartilage, parameters that are influenced by cartilage composition. These parameters were measured in native and GAG-depleted cartilage in order to estimate the bounds on the values one might expect for cartilage in arbitrary states of degeneration. The range of T(o)(1) was 0.3 sec; the range of r was 0.6 (mM*s)(-1) at 8.5 T and 1.4 (mM*s)(-1) at 2 T. These data suggest that Gd(DTPA)(2-) will be underestimated (and GAG overestimated) if the values for T(o)(1) and r are assumed to be those of native cartilage. (For example, in a severe case a 90% loss of GAG would be underestimated as a 70% loss.) Gd(HPDO3A) was investigated as a nonionic "control agent" and found to have relaxivity and diffusion properties that were comparable to Gd(DTPA)(2-) (r(Gd(HPDO3A))/r(Gd(DTPA)) approximately 1; D(Gd(HPDO3A))/D(Gd(DTPA)) approximately 0.85). Since Gd(HPDO3A) distributes uniformly through cartilage (independent of GAG), the distribution of T(1) with Gd(HPDO3A) can be used as a surrogate measure of variations in T(o)(1) and r, if present. From the perspective of transport, if Gd(HPDO3A) has fully penetrated the cartilage, Gd(DTPA)(2-) would have in the same time frame. Therefore, the data confirm the efficacy of using Gd(HPDO3A) as a "control agent" for dGEMRIC.     

Reproducibility of dGEMRIC in assessment of hip joint cartilage: A prospective study

Purpose

To investigate the reproducibility of dGEMRIC in the assessment of cartilage health of the adult asymptomatic hip joint.

Materials and Methods

Fifteen asymptomatic volunteers (mean age, 26.3 years ± 3.0) were preliminarily studied. Any volunteer that was incidentally diagnosed with damaged cartilage on MRI (n = 5) was excluded. Ten patients that had no evidence of prior cartilage damage (mean age, 26.2 years ± 3.4) were evaluated further in this study. The reproducibility of dGEMRIC was assessed with two T1_Gd exams performed 4 weeks apart in these volunteers. The protocol involved an initial standard MRI to confirm healthy cartilage, which was then followed by dGEMRIC. The second scan included only the repeat dGEMRIC. Region of interest (ROI) analyses for T1_Gd‐measurement was performed in seven radial reformats. Statistical analysis included the student's t‐test and intra‐class correlation (ICC) measurement to assess reproducibility.

Results

Overall 70 ROIs were studied. Mean cartilage T1_Gd values at various loci ranged from 560.9 ms to 684.4 ms at the first set of readings and 551.5 ms to 662.2 ms in the second one. The mean difference per region of interest between the two T1_Gd‐measurements ranged from 21.4 ms (3.7%) to 45.0 ms (6.8%), which was not found to be statistically significant (P = 0.153). There was a high reproducibility detected (ICC range, 0.667–0.915). Intra‐ and Inter‐observer analyses proved a high agreement for T1_Gd assessment (0.973 and 0.932).

Conclusion

We found dGEMRIC to be a reliable tool in the assessment of cartilage health status in adult hip joints. J. Magn. Reson. Imaging 2009;30:224–228. © 2009 Wiley‐Liss, Inc.     

High‐risk nodules detected in the hepatobiliary phase of Gd‐EOB‐DTPA‐enhanced mr imaging in cirrhosis or chronic hepatitis: Incidence and predictive factors for hypervascular transformation,preliminary results

Purpose:

To evaluate the incidence and predictive factors of hypervascular transformation during follow‐up of “high‐risk nodules” detected in the hepatobiliary phase of initial Gd‐EOB‐DTPA‐enhanced MRI in chronic liver disease patients.

Materials and Methods:

A total of 109 patients with chronic liver disease who underwent Gd‐EOB‐DTPA‐enhanced MRI several times were investigated. Of these, 43 patients had 76 high‐risk nodules with both hypointensity in the hepatobiliary phase and hypovascularity in the arterial phase of initial MRI. These nodules were observed until hypervascularity was detected. MRI and clinical findings were compared to assess the incidence and potential predictive factors for hypervascular transformation between the group showing hypervascular transformation and the group not showing hypervascularization.

Results:

The median observation period was 242.5 ± 203.2 days (range, 47–802 days). Overall, 24 of 76 high‐risk nodules (31.6%) showed hypervascular transformation during follow‐up (median observation period, 186.0 ± 190.3 days). The growth rate of the nodules (P < 0.001), the presence of fat within nodules (P = 0.037), and hyperintensity on T1‐weighted images (P = 0.018) were significantly correlated with hypervascularization.

Conclusion:

Subsets of high‐risk nodules tended to show hypervascular transformation during follow‐up, with an increased growth rate, the presence of fat, and hyperintensity on T1‐weighted images as predictive factors. J. Magn. Reson. Imaging 2013;37:1377–1383. © 2013 Wiley Periodicals, Inc.     

Evaluation of neovessels in atherosclerotic plaques of rabbits using an albumin-binding intravascular contrast agent and MRI

Purpose

To test whether B‐22956/1, a novel intravascular contrast agent with a high affinity to serum albumin (Bracco Imaging SpA.), allowed quantifying neovessel and macrophage density in atherosclerotic plaques of rabbits using MRI.

Materials and Methods

A T1‐weighted MRI of the aorta was acquired in 10 rabbits (7 atherosclerotic and 3 control rabbits) before and up to 2 h after intravenous injection of 100 μmol/kg of Gd‐DTPA or 75 μmol/kg of B‐22956/1. Plaque enhancement was measured at different time points. Immunohistochemistry was performed using anti‐CD 31 antibodies and anti‐RAM 11 antibodies to correlate to neovessel and macrophage density, respectively.

Results

MRI showed a significant plaque enhancement 2 h after B‐22956/1 versus Gd‐DTPA in the atherosclerotic group (39.75% versus 9.5%; P < 0.0001. Early atherosclerotic plaques (n = 146) enhancement positively correlates with neovessel density on corresponding histological sections (r = 0.42; P < 0.01). Enhancement of atherosclerotic plaques 2 h after injection of B‐22956/1 correlated with macrophage density (r = 0.71; P < 0.01).

Conclusion

Enhancement of atherosclerotic plaques with MRI correlated with neovessel density at early time points after the injection of B‐22956/1 and with macrophage density, at later time points. Hence, B‐22956/1‐enhanced MRI represents a promising imaging technique for the identification of “high‐risk” plaques. J. Magn. Reson. Imaging 2008;27:1406–1411. © 2008 Wiley‐Liss, Inc.     

Gadoxetic acid disodium-enhanced magnetic resonance imaging for biliary and vascular evaluations in preoperative living liver donors: comparison with gadobenate dimeglumine-enhanced MRI

Purpose

To compare gadoxetic acid disodium (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) with gadobenate dimeglumine (Gd‐BOPTA)‐enhanced MRI in preoperative living liver donors for the evaluation of vascular and biliary variations.

Materials and Methods

Sixty‐two living liver donors who underwent preoperative MRI were included in this study. Thirty‐one patients underwent MRI with Gd‐EOB‐DTPA enhancement, and the other 31 underwent MRI with Gd‐BOPTA enhancement. Two abdominal radiologists retrospectively reviewed dynamic T1‐weighted and T1‐weighted MR cholangiography images and ranked overall image qualities for the depiction of the hepatic artery, portal vein, hepatic vein, and bile duct on a 5‐point scale and determined the presence and types of normal variations in each dynamic phase. Semiquantitative analysis for bile duct visualization was also conducted by calculating bile duct‐to‐liver contrast ratios.

Results

No statistical differences were found between the two contrast media in terms of hepatic artery or bile duct image quality by the two reviewers, or in terms of portal vein image quality by one reviewer (P > 0.05). Gd‐BOPTA provided better image qualities than Gd‐EOB‐DTPA for the depiction of hepatic veins by both reviewers, and for the depiction of portal veins by one reviewer (P < 0.01). The two contrast media‐enhanced images had similar bile duct‐to‐liver contrast ratios (P > 0.05). Regarding diagnostic accuracies with hepatic vascular/biliary branching types, no significant differences were observed between the two contrast media (P > 0.05).

Conclusion

Gd‐EOB‐DTPA could be as useful as Gd‐BOPTA for the preoperative evaluation of living liver donors, and has the advantage of early hepatobiliary phase image acquisition. J. Magn. Reson. Imaging 2011;33:149–159. © 2010 Wiley‐Liss, Inc.     

In vivo qualitative assessments of articular cartilage in the rabbit knee with high-resolution MRI at 3 T.

Proteoglycan (PG) loss and disruption of the collagen framework in cartilage are early events associated with osteoarthritis (OA). The feasibility of in vivo high-resolution MRI assessments probing both macromolecules was explored in articular cartilage of the rabbit knee. One-millimeter thick coronal images were obtained at 3 T with a 97 x 97 microm(2) pixel size. A 22% decrease in the magnetization transfer (MT) exchange rate along with an approximately 2-fold greater Gd(DTPA)(2-)-induced decrease in T(1) relaxation time were measured in response to papain injection 1 day prior to the MRI session, indicative of an alteration of collagen integrity and PG depletion, respectively. A two-point method was tested as an alternative to the more time-consuming multipoint method typically used to measure T(1) changes. Kinetics of Gd(DTPA)(2-) uptake were observed with a 10-min time resolution. The diffusive transport of Gd(DTPA)(2-) was characterized by a T(1) decrease approximately 2-fold faster in papain-treated knees. These data suggest that kinetics of tracer diffusion may be used as an informative marker of PG loss, in addition to the amplitude of T(1) variations. When applied to a relevant OA model, the combination of MT and Gd(DTPA)(2-)-MRI may help in identifying new active compounds during efficacy studies on cartilage protection.     

Quantitative assessment of intervertebral disc glycosaminoglycan distribution by gadolinium-enhanced MRI in orthopedic patients.

Our hypothesis was that the enhanced MRI of cartilage (dGEMRIC) imaging protocol could be used in patients to quantify the sulfated glycosaminoglycan (sGAG) in intervertebral discs (IVD). To test this hypothesis, 23 patients with degenerative disc pathology scheduled for surgery were studied by a specific dGEMRIC protocol: each patient underwent two MRI scans, before and 3.5 hr after Gd(DTPA)2-injection of a nonconventional dose of 40 mL. Then, T(1PRE-ENH) and T(1POST-ENH) parametric images of the disc were obtained, from which a new index DeltaT(1) of the molecular status of the IVD was computed (T(1PRE-ENH) - T(1POST-ENH)). A total of 31 tissue samples (one or two from each patient) obtained at herniectomy were collected and biochemically analyzed for sGAG content and used as the gold standard for comparison. DeltaT(1) values in correspondence to degenerated sectors were higher (158 +/- 36 ms) compared to normal sectors (80 +/- 13 ms). Linear regression analysis between MRI-derived and biochemistry-derived measurements resulted in a significant correlation (r = 0.73, P < 0.0001). The DeltaT(1) parametric images, calculated using the modified dGEMRIC technique, provided noninvasive quantitative information about sGAG content within discal tissue in vivo, which resulted in agreement with biochemical analysis. The application of this new MRI method could provide diagnostic information for standard treatment of lumbar discopathy and for innovative therapies of regenerative medicine.     

Longitudinal analysis of MRI T2 knee cartilage laminar organization in a subset of patients from the osteoarthritis initiative

The purpose of this pilot study was to longitudinally quantify the T₂ laminar integrity of knee cartilage in a subset of subjects with osteoarthritis from the Osteoarthritis Initiative at baseline, 1‐year follow‐up, and 2‐year follow‐up. Cartilage from 13 subjects was divided into six compartments and subdivided into deep and superficial layers. At each time point, mean T₂ values in superficial and deep layers were compared. Longitudinal analysis included full‐thickness mean T₂, mean deep T₂, mean superficial T₂, mean T₂ laminar difference, mean percentage T₂ laminar difference, and two‐dimensional measures of cartilage thickness. More compartments showed significantly higher superficial T₂ than deep T₂ values at baseline and 1‐year follow‐up compared to 2‐year follow‐up. No significant longitudinal changes of full‐thickness mean T₂ and superficial T₂ values were observed. Significant longitudinal changes were observed in the deep T₂ values, T₂ laminar difference, and percentage T₂ laminar difference. Cartilage thickness had no influence on T₂ analysis. Results of this study suggest that laminar analysis may improve the sensitivity to detect longitudinal T₂ changes and that disruption of the T₂ laminar organization of knee cartilage may be present in knee osteoarthritis progressors. Further investigation is warranted to evaluate the potential of the presented methodology to better characterize evolution and pathophysiology of osteoarthritis. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Interstitial MR lymphography in mice with gadopentetate dimeglumine and gadoxetate disodium

Purpose

To investigate the utility of interstitial MR lymphography with gadopentetate dimeglumine (Gd‐DTPA) or gadoxetate disodium (Gd‐EOB‐DTPA) in mice.

Materials and Methods

We performed MR lymphography after the subcutaneous injection of Gd‐DTPA or Gd‐EOB‐DTPA (0.1, 0.5, or 2.0 μmol per mouse) into the right footpad in six healthy mice, and the time courses of contrast enhancement were assessed. Additionally, the lymphatic pathways from two distinct sites were assessed in tandem by interstitial MR lymphography studies.

Results

Subcutaneous injection of Gd‐DTPA or Gd‐EOB‐DTPA caused lymph node enhancement immediately after injection, followed by a rapid decline. Dose dependency was shown for the lymph node enhancement, and a high‐dose injection caused prominent visualization of the veins. Lymph node enhancement did not differ significantly between Gd‐DTPA and Gd‐EOB‐DTPA or between Gd‐EOB‐DTPA premixed and not premixed with bovine serum albumin. The tandem assessment of two lymphatic pathways was feasible, and image fusion aided detailed comparison.

Conclusion

Interstitial MR lymphography with Gd‐DTPA or Gd‐EOB‐DTPA allowed clear visualization of the lymphatic pathway in healthy mice, and no significant difference was found between the two agents. Their rapid kinetics limits the imaging timing window, however, facilitates repeated assessment in a single imaging session. J. Magn. Reson. Imaging 2011;33:490–497. © 2011 Wiley‐Liss, Inc.