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Biochemical MRI in Musculoskeletal Applications Technology Tissue function Biochemical MRI in Musculoskeletal Applications Siegfried Trattnig; Štefan Zbýň; Vladimir Juras; Pavol Szomolanyi; Stephan Domayer; Iris-Melanie Noebauer-Huhmann; Goetz Welsch; Benjamin Schmitt MR Centre – High field MR, Department of Radiology, Medical University of Vienna/Vienna General Hospital, Vienna, Austria 1. Biochemical MRI assessment 1.1) Proteoglycan-sensitive MRI exchange-dependent saturation transfer of cartilage and cartilage techniques (CEST) [6]. Of these techniques, only repair Although no MRI sequence is really dGEMRIC has so far become clinically use- To visualize the constitution of articular 100% specific for only proteoglycans or ful in cartilage repair imaging. cartilage and cartilage repair tissue, collagens, there are MRI methods that a variety of different MRI methods are reportedly focus mainly on one compo- a) Delayed gadolinium-enhanced MRI available. Considering the composition nent of articular cartilage. The nega- of cartilage (dGEMRIC*) of healthy hyaline articular cartilage, tively-charged proteoglycan, composed GAG are important to the cartilage tissue’s these methods can depict relatively spe- of a central core protein to which GAG biochemical and biomechanical func- cifically either one component of carti- are bound, can be visualized by delayed tion. GAG are the main source of fixed lage or a combination of different com- gadolinium-enhanced MRI of cartilage charge density (FCD) in cartilage, and ponents. Although some more recent (dGEMRIC*) [3], sodium MR imaging are often decreased in the early stages techniques, in particular CEST, have not [4, 5], and, very recently, chemical of cartilage degeneration [7], or in repar- yet been validated sufficiently, studies have shown promising initial results. Articular cartilage is complex, dense, 1A 1 (1A) Shows a sagittal connective tissue that relies on the dif- 3D GRE image in a patient fusion of solutes for nutrition [1]. after microfracturing at 3T. Responsible for the biomechanical prop- In the area of microfracture erties of articular cartilage is the extra- only slight thinning of the cartilage layer can be seen. cellular matrix, mainly composed of (1B) Precontrast* T1-map water (~75%), collagen (~20%), and shows no difference in proteoglycan aggregates (~5%) [1, 2]. T1 relaxation times in the Water either freely moves throughout repair tissue; however, in the matrix or is bound to macromole- the postcontrast* image (1C) a significant drop in cules. Collagen in hyaline cartilage is T1 values in the repair largely type II, which creates a stable tissue can be seen, which network throughout the cartilage. The corresponds to a low gly- negatively-charged proteoglycans are cosaminoglycan content. composed of a central core protein to which glycosaminoglycans (GAG) are bound. 86 MAGNETOM Flash · 2/2012 · www.siemens.com/magnetom-world Tissue function Technology ative cartilage after cartilage repair [8]. requires a break in between the two b) 23Na (Sodium) imaging of cartilage Intravenously administered gadolinium MRI scans, where the contrast agent The major advantage of sodium MRI in diethylenetriamine pentaacetate anion, must be administered and a delay of at musculoskeletal applications is that it (Gd-DTPA2-) penetrates the cartilage through least 90 minutes after injection is needed is highly specific for glycosaminoglycan both the articular surface and the sub- for penetration of the contrast agent content, and, since the sodium from chondral bone. The contrast equilibrates into the cartilage. Scan time reduction, surrounding structures in the joint is low in inverse relation to the FCD, which is, compared to the standard inversion (< 50 mM), cartilage can be visualized in turn, directly related to the GAG con- recovery (IR) evaluation, has been with very high contrast without the centration. Therefore, T1, which is deter- achieved with a new approach using fast requirement for any exogenous contrast mined by the Gd-DTPA2- concentration, T1-mapping based on GRE-technique agent, such as with dGEMRIC*. becomes a specific measure of tissue [12]. Although the 90-minute delay is The recent proliferation of 7T1 whole- GAG concentration, suggesting that still required, this might increase the body MRI scanners in clinical research Gd-DTPA2- enhanced MRI has the poten- clinical applicability of the dGEMRIC* centers has had a significant impact on tial to monitor the GAG content of carti- technique. Other drawbacks of dGEMRIC* sodium MRI and its potential for clinical lage in vivo [9]. Thus, T1-mapping, are the use of i. v. contrast agent admin- use. Since signal-to-noise (SNR) scales enhanced by delayed administration of istration, the necessity of a double dose linearly with increasing field strength, 2- Gd-DTPA (T1 dGEMRIC*), can be con- of contrast agent, and the fact that and because of the lack of B1 penetration sidered the most widely used methodol- uptake and distribution of contrast agent and B0 susceptibility that pose problems ogy for detecting proteoglycan depletion is not only dominated by GAG. with proton imaging, sodium MRI can in articular cartilage (Fig. 1), and has Since GAG content is responsible for be particularly advantageous at higher shown promising results [10, 11]. cartilage function, particularly its tensile fields. The low gyromagnetic ratio of As differences in pre-contrast values strength, the monitoring of the develop- sodium also means significantly lower between cartilage repair tissue and nor- ment of GAG content in cartilage repair power deposition compared with proton mal hyaline cartilage are larger compared tissues may provide information about imaging, which thus reduces SAR prob- to early cartilage degeneration, in carti- the quality of the repair tissue. A study lems at 7T1. It is, therefore, very likely lage repair tissue, the pre-contrast T1 by our group showed that dGEMRIC* that the improved SNR sodium MRI at values must also be calculated [8]. The was able to differentiate between differ- 7T1 can provide a robust tool for quan- concentration of GAG is represented by ent cartilage repair tissues with higher titative imaging of MSK structures in delta ΔR1, i.e., the difference in relax- delta ΔR1 values, and thus, lower GAG particular cartilage. Although sodium ation rate (R1=1/T1) between T1precontrast content, in cartilage repair tissue after MRI has high specificity and does not and T1postcontrast. Thus, the sequence must MFX, compared to MACT [13]. The appli- require any exogenous contrast agent, be performed twice, for pre-contrast cability of this technique has also been it does require special hardware capa- and delayed post-contrast T1-mapping. shown in regions other than the knee bilities (multinuclear) and specialized This increases the total scan time, and joint [14–16]. RF coils [5]. 1B 1C MAGNETOM Flash · 2/2012 · www.siemens.com/magnetom-world 87 Technology Tissue function 2A 2B With the application of a 7T whole-body MACT (p = .002) repair tissue, compared is transplanted, and in patients after system and a modified 3D GRE opti- to reference cartilage. These differences patella dislocation, have demonstrated mized for sodium imaging and dedicated were influenced by surgery type, but not the potential of sodium imaging in the multi-element sodium coils, we per- by age and follow-up interval. Although detection of early stages of cartilage formed a series of clinical studies. sodium SNR was not different between degeneration [19]. In a small group of 12 patients after the reference cartilage in the MACT and matrix-associated autologous chondro- BMS patients (p = .528), it was signifi- c) Chemical Exchange Saturation cyte transplantation (MACT), sodium cantly higher in MACT than in BMS repair Transfer (CEST) imaging enabled the differentiation tissue (p = .002). There was no differ- Chemical exchange between bulk water between sodium content, and thus GAG ence between the magnetic resonance protons and protons bound to solutes in the transplants, compared to native, observation of cartilage repair tissue can be visualized with MR imaging [20] healthy cartilage. In all patients, the (MOCART) scores for MACT and BMS by using the saturation transfer (ST) sodium SNR was lower in the repair tis- patients (p = .889). No correlation was technique, a common approach in sue compared to healthy cartilage. observed between the MOCART score nuclear magnetic resonance (NMR) [21]. A good correlation between sodium and repair tissue SNR with sodium imag- Consequently, the corresponding MR imaging and dGEMRIC* in the quantifi- ing (R = .111). Our results suggest that imaging scheme is referred to as CEST cation of GAG content was found in MACT provides higher GAG content and, MRI [22, 23]. In principle, CEST MRI patients after MACT [17]. therefore, higher-quality repair tissue relies on a reduction of bulk water MR In another study, 18 patients who had compared to the BMS techniques. Sodium signal as a consequence of selective sat- different cartilage repair surgeries (nine MR imaging at 7T1 (Fig. 2) might be uration of off-resonant (solute) spins bone marrow stimulation (BMS) and beneficial in the non-invasive evaluation and subsequent chemical transfer of the nine MACT patients), age-matched, with of cartilage repair procedure efficacy in saturation to spins of bulk water [24]. similar postoperative intervals and the knee [18]. A prerequisite for observation of CEST defect locations, were examined with Similar studies in patients after long-term phenomena within a chemical environ- sodium imaging. Sodium SNR was signif- autologous osteochondral transplanta- ment is the abundance of sufficiently icantly lower in BMS (p < .001) and tion (AOT) in which hyaline cartilage labile solute protons that are in contact 88 MAGNETOM Flash · 2/2012 · www.siemens.com/magnetom-world Tissue function Technology 2C 2 Sagittal images of the knee of a 43-year-old woman obtained 42 months after 400 MFX cartilage repair proce- dure. The proton-density- weighted 2D-TSE image with fat suppression (2A), sodium 3D-GRE image (2B), and color- 300 coded sodium 3D-GRE image (2C). The cartilage repair tis- sue is situated between the two arrows. Color scale repre- sents the sodium signal inten- sity values.
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