Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

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: T(1) 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 T(1) 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-DTPA(2) transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd-DTPA(2) will yield a falsely too long T(1) . J. Magn. Reson. Imaging 2011;. © 2011 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: T(1) 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 T(1) 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-DTPA(2) transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd-DTPA(2) will yield a falsely too long T(1) . J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc

Feasibility for mapping cartilage t1 relaxation times in the distal metacarpus3/metatarsus3 of thoroughbred racehorses using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dgemric): normal cadaver study

Osteoarthritis of the metacarpo/metatarsophalangeal joints is one of the major causes of poor performance in horses. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) may be a useful technique for noninvasively quantifying articular cartilage damage in horses. The purpose of this study was to describe dGEMRIC characteristics of the distal metacarpus3/metatarsus3 (Mc3/Mt3) articular cartilage in 20 cadaver specimens collected from normal Thoroughbred horses. For each specimen, T1 relaxation time was measured from scans acquired precontrast and at 30, 60, 120, and 180 min post intraarticular injection of Gd-DTPA(2-) (dGEMRIC series). For each scan, T1 relaxation times were calculated using five regions of interest (sites 1-5) in the cartilage. For all sites, a significant decrease in T1 relaxation times occurred between precontrast scans and 30, 60, 120, and 180 min scans of the dGEMRIC series (P < 0.0001). A significant increase in T1 relaxation times occurred between 60 and 180 min and between 120 and 180 min post Gd injection for all sites. For sites 1-4, a significant increase in T1 relaxation time occurred between 30 and 180 min postinjection (P < 0.05). Sites 1-5 differed significantly among one another for all times (P < 0.0001). Findings from this cadaver study indicated that dGEMRIC using intraarticular Gd-DTPA(2-) is a feasible technique for measuring and mapping changes in T1 relaxation times in equine metacarpo/metatarsophalangeal joint cartilage. Optimal times for postcontrast scans were 60-120 min. Future studies are needed to determine whether these findings are reproducible in live horses. (C) 2013 Veterinary Radiology & Ultrasound

Is cartilage sGAG content related to early changes in cartilage disease? Implications for interpretation of dGEMRIC.

OBJECTIVE: This study investigates sulphated glycosaminoglycans (sGAG) content changes in early osteoarthritis (OA), and whether contrast-enhanced magnetic resonance imaging (MRI) of cartilage in vitro may identify early event of OA pathology. METHOD: Osteochondral plugs from patients with hip OA or femoral neck fracture (reference group) were collected and analysed by 1.5 T MRI with ΔR1 as a measure of cartilage contrast concentration. Cartilage hydration, contents of sGAG, cartilage oligomeric matrix protein (COMP), hydroxyproline, denatured collagen, and aggrecan TEGE(392) neoepitope were determined and histological grading was performed. RESULTS: sGAG content correlated to ΔR1, although no difference in either of these parameters was detectable between OA and reference cartilage at 4 h of contrast equilibration. In contrast, biochemical analysis of other cartilage matrix constituents showed distinct alterations typical for early cartilage degradation in OA cartilage and with clear evidence for increased aggrecan turnover. CONCLUSION: In the present in vitro study, cartilage sGAG content could not distinguish between early OA cartilage and reference cartilage. Given, that delayed gadolinium enhanced MRI of cartilage (dGEMRIC) indicates early events in the pathogenesis of OA in vivo, our results from the in vitro studies imply other, additional factors than cartilage sGAG content, e.g., alterations in diffusion or increased supply of contrast agent in the diseased joint. Alternatively, an altered dGEMRIC reflects later stages of OA, when sGAG content decreases. Further investigations are warranted, to understand variations in sGAG content in pathology, an essential background for interpreting dGEMRIC measurements

Validation Of Delayed Gadolinium-Enhanced Magnetic Resonance Imaging Of Cartilage And T2 Mapping For Quantifying Distal Metacarpus/Metatarsus Cartilage Thickness In Thoroughbred Racehorses

The purpose of this study was to determine whether delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping are accurate techniques for measuring cartilage thickness in the metacarpus3/metatarsus3 (Mc3/Mt3) of Thoroughbred racehorses. Twenty-four Mc3/Mt3 cadaver specimens were acquired from six healthy racehorses. Cartilage thickness was measured from postintra-articular Gd-DTPA2 images acquired using short tau inversion recovery (STIR), and proton density weighted (PDw) sequences, and compared with cartilage thickness measured from corresponding histologic images. Two observers performed each histologic measurement twice at three different sites, with measurement times spaced at least 5 days apart. Histologic cartilage thickness was measured at each of the three sites from the articular surface to the bonecartilage interface, and from the articular surface to the mineralized cartilage interface (tidemark). Intra-observer repeatability was good to moderate for dGEMRIC where Mc3/Mt3 cartilage was not in contact with the proximal phalanx. Where the Mc3/Mt3 cartilage was in contact with the proximal phalanx cartilage, dGEMRIC STIR and T2 mapping PDw cartilage thicknesses of Mc3/Mt3 could not be measured reliably. When measured from the articular surface to the bonecartilage interface, histologic cartilage thickness did not differ from STIR or PDw cartilage thickness at the site where the Mc3/Mt3 cartilage surface was separated from the proximal phalanx cartilage (P > 0.05). Findings indicated that dGEMRIC STIR and T2 mapping PDw are accurate techniques for measuring Mc3/Mt3 cartilage thickness at locations where the cartilage is not in direct contact with the proximal phalanx cartilage

Quantitative MRI of Human Cartilage In Vivo : Relationships with Arthroscopic Indentation Stiffness and Defect Severity

Objective. To investigate the association of cartilage defect severity, as determined by the International Cartilage Repair Society (ICRS) grading with indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI), a biomarker for the integrity of articular cartilage. Design. Twenty-one patients scheduled for arthroscopic were included in the study. Prior to arthroscopy, subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which also included ICRS grading and measurement of arthroscopic indentation stiffness. Arthroscopic evaluations and T2 mapping at anterior, central, and posterior medial and lateral femoral condyles were correlated using a colocalization scheme. Differences in Young's modulus, as derived by indentation tests, and T2 times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis H tests. The correlation between modulus and T2 times was analyzed using Spearman's rank correlation coefficients. Results. Modulus and T2 showed significant topographical variation. In the anterior region of interest (ROI) on the medial condyle the modulus showed a negative association with ICRS grade (P = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and 1 (P = 0.047). Similar, but nonsignificant associations were found in the central ROI on the medial condyle. No significant correlations were observed between the indentation modulus and T2 times. Conclusions. Cartilage degeneration is identified both with mechanical indentation and T2 mapping in MRI. However, in this study, indentation stiffness and T2 relaxation time in vivo, were not associated.Peer reviewe