A practical guide to imaging of cartilage repair with emphasis on bone marrow changes

Orthopedic surgeons have multiple options available to treat articular cartilage lesions, including microfracture, osteochondral autografting, and autologous chondrocyte implantation. By having basic knowledge of these surgical procedures, radiologists can more accurately interpret imaging studies obtained after surgery. In this article, we briefly review the different types of cartilage repair procedures, their appearance on magnetic resonance imaging (MRI), and pathologic MRI findings associated with postoperative complications. We also briefly discuss advanced MRI techniques (T2 mapping, delayed gadolinium-enhanced MRI of cartilage, sodium MRI) that have been recently used to assess the biochemical composition of repair tissue matrix. MRI can accurately assess the status and health of cartilage repair tissue. By providing this information to orthopedic surgeons, radiologists can play a valuable role in the management of patients who undergo cartilage repair surgery.     

定量MRI技术在跑步人群膝关节软骨中的应用进展

膝关节软骨作为膝关节最重要的结构之一,在维持膝关节正常运动中具有非常关键的作用。适度合理的跑步对关节软骨有着积极健康的作用,可以有效减少关节疾病,而不合理的跑步会增加膝关节软骨损伤和退变风险。在常规MRI基础上发展起来的T_1ρ、T₂ mapping、T₂* mapping、T₁ mapping、扩散张量成像及软骨延迟动态增强MRI等定量MRI新技术,不仅可以优化显示膝关节软骨的形态改变、组织构成及超微结构的改变,还可为损伤的诊断提供丰富的定量信息,对指导跑步人群的运动具有重要意义。就不同定量MRI技术对跑步相关的膝关节软骨变化的研究进展予以综述。     

Review of Quantitative Knee Articular Cartilage MR Imaging

Osteoarthritis (OA) is one of the most prevalent disorders in today’s society, resulting in significant socio-economic costs and morbidity. MRI is widely used as a non-invasive imaging tool for OA of the knee. However, conventional knee MRI has limitations to detect subtle early cartilage degeneration before morphological changes are visually apparent. Novel MRI pulse sequences for cartilage assessment have recently received increased attention due to newly developed compositional MRI techniques, including: T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), sodium MRI, diffusion-weighted imaging (DWI)/ diffusion tensor imaging (DTI), ultrashort TE (uTE), and glycosaminoglycan specific chemical exchange saturation transfer (gagCEST) imaging. In this article, we will first review these quantitative assessments. Then, we will discuss the variations of quantitative values of knee articular cartilage with cartilage layer (depth)- and angle (regional)-dependent approaches. Multiple MRI sequence techniques can discern qualitative differences in knee cartilage. Normal articular hyaline cartilage has a zonal variation in T2 relaxation times with increasing T2 values from the subchondral bone to the articular surface. T1rho values were also higher in the superficial layer than in the deep layer in most locations in the medial and lateral femoral condyles, including the weight-bearing portion. Magic angle effect on T2 mapping is clearly observed in the both medial and lateral femoral condyles, especially within the deep layers. One of the limitations for clinical use of these compositional assessments is a long scan time. Recent new approaches with compressed sensing (CS) and MR fingerprinting (MRF) have potential to provide accurate and fast quantitative cartilage assessments.     

Initial results of in vivo high-resolution morphological and biochemical cartilage imaging of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle

Objective  The aim of this study was to use morphological as well as biochemical (T2 and T2* relaxation times and diffusion-weighted imaging (DWI)) magnetic resonance imaging (MRI) for the evaluation of healthy cartilage and cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle joint. Materials and methods  Ten healthy volunteers (mean age, 32.4 years) and 12 patients who underwent MACT of the ankle joint (mean age, 32.8 years) were included. In order to evaluate possible maturation effects, patients were separated into short-term (6–13 months) and long-term (20–54 months) follow-up cohorts. MRI was performed on a 3.0-T magnetic resonance (MR) scanner using a new dedicated eight-channel foot-and-ankle coil. Using high-resolution morphological MRI, the magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. For biochemical MRI, T2 mapping, T2* mapping, and DWI were obtained. Region-of-interest analysis was performed within native cartilage of the volunteers and control cartilage as well as cartilage repair tissue in the patients subsequent to MACT. Results  The overall MOCART score in patients after MACT was 73.8. T2 relaxation times (~50 ms), T2* relaxation times (~16 ms), and the diffusion constant for DWI (~1.3) were comparable for the healthy volunteers and the control cartilage in the patients after MACT. The cartilage repair tissue showed no significant difference in T2 and T2* relaxation times (p ≥ 0.05) compared to the control cartilage; however, a significantly higher diffusivity (~1.5; p < 0.05) was noted in the cartilage repair tissue. Conclusion  The obtained results suggest that besides morphological MRI and biochemical MR techniques, such as T2 and T2* mapping, DWI may also deliver additional information about the ultrastructure of cartilage and cartilage repair tissue in the ankle joint using high-field MRI, a dedicated multichannel coil, and sophisticated sequences.     

T1ρ MRI of human musculoskeletal system

Magnetic resonance imaging (MRI) offers the direct visualization of the human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI techniques based on T₁‐ and T₂‐weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage, with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article we focus on cartilage biochemical composition, basic principles of T_1ρ MRI, implementation of T_1ρ pulse sequences, biochemical validation, and summarize the potential applications of the T_1ρ MRI technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we also review the potential advantages, challenges, and future prospects of T_1ρ MRI for widespread clinical translation. J. Magn. Reson. Imaging 2015;41:586–600. © 2014 Wiley Periodicals, Inc.     

Accelerating MR parameter mapping using sparsity‐promoting regularization in parametric dimension

MR parameter mapping requires sampling along additional (parametric) dimension, which often limits its clinical appeal due to a several‐fold increase in scan times compared to conventional anatomic imaging. Data undersampling combined with parallel imaging is an attractive way to reduce scan time in such applications. However, inherent SNR penalties of parallel MRI due to noise amplification often limit its utility even at moderate acceleration factors, requiring regularization by prior knowledge. In this work, we propose a novel regularization strategy, which uses smoothness of signal evolution in the parametric dimension within compressed sensing framework (p‐CS) to provide accurate and precise estimation of parametric maps from undersampled data. The performance of the method was demonstrated with variable flip angle T₁ mapping and compared favorably to two representative reconstruction approaches, image space‐based total variation regularization and an analytical model‐based reconstruction. The proposed p‐CS regularization was found to provide efficient suppression of noise amplification and preservation of parameter mapping accuracy without explicit utilization of analytical signal models. The developed method may facilitate acceleration of quantitative MRI techniques that are not suitable to model‐based reconstruction because of complex signal models or when signal deviations from the expected analytical model exist. Magn Reson Med 70:1263–1273, 2013. © 2012 Wiley Periodicals, Inc.     

Quantitative parametric MRI of articular cartilage: a review of progress and open challenges

With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T₁, T₂ and T_1ρ relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.The treatment of the degenerative joint disease osteoarthritis (OA) remains problematic. For advanced end-stage “whole organ” disease the only viable treatment option is joint replacement where feasible. For earlier stage OA, disease progression is unpredictable and often slow, which makes it very difficult to evaluate agents that have possible disease-modifying properties. Although the OA disease process may commence within any joint structure including ligaments, bone, meniscus or articular cartilage, the advancement of disease is inevitably associated with progressive cartilage attrition and inexorable functional deterioration. The non-invasive assessment of tissue damage (at a stage in the disease process where tissue damage is potentially reversible) and the ability to monitor its repair during and following treatment is central to the future development of novel therapies aimed at arresting or reversing cartilage destruction.The purpose of this review is to evaluate current and emerging quantitative MR protocols for assessment of cartilage in order to identify the open challenges that will drive further development in the field. Of specific interest are the methods that can detect the initial stages of cartilage degradation and also those that allow the biomechanical properties of cartilage to be studied. Such techniques might be important aids for early diagnosis of arthritic diseases and also in assessing the progress of regenerative and reparative therapies for OA in vivo [1,2]. An ideal scenario would be the development of high-resolution whole body MRI methods that could provide functional information about the state of cartilage at multiple sites, in a timely and cost-effective fashion, without resort to exogenous contrast agents. This is particularly challenging for the assessment of cartilage because high spatial resolution is required. We will discuss what degree of progress has been made towards that lofty goal where MRI biomarkers could be used to reliably identify and characterise early cartilage damage or sites at risk of cartilage loss.     

微骨折术治疗膝关节软骨损伤修复效果T2 star mapping评价研究

目的 本研究应用MRI对关节镜下微骨折法治疗膝关节软骨损伤修复效果进行大体组织形态学评估及定量分析.方法 本研究纳入14例有膝关节软骨损伤症状并接受关节镜下微骨折法治疗的病例进行回顾性病例分析.所有病例的关节软骨损伤均为ICRS分级Ⅲ或Ⅳ,术中测量病变面积为2～8cm^2.1年随访期内所有病例都接受常规MRI序列及T2 star mapping序列扫描（1.5T）.对损伤修复区域采用软骨组织修复磁共振观察评分系统（MOCART）进行评价.采用T2 star mapping序列扫描图像感兴趣区划分的方法对修复区域及自身正常软骨所测量的T2＊弛豫值进行分析比较.结果 1年随访期软骨修复区MOCART评分为59.50±23.90,相邻本体软骨组织评分为65.21±21.84,与软骨修复组间比较无显著差异.软骨修复区和邻近正常自体软骨组织T2＊弛豫时间分别为（31.14±9.26）ms和（32.93±11.69）ms,修复区软骨组织质地与正常软骨组织相近.结论 经关节镜下微骨折法修复膝关节软骨损伤后1年随访观察期内,MRI软骨扫描可见软骨损伤区填充良好.经T2＊测量值分析证实软骨修复组织可以达到与邻近正常透明软骨相近的组织结构.     

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage: topographical variation and relationships to mechanical properties.

The macromolecular structure and mechanical properties of articular cartilage are interrelated and known to vary topographically in the human knee joint. To investigate the potential of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness cartilage disks were prepared from six anatomical locations in nonarthritic human knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were determined with the use of unconfined compression tests, followed by quantitative MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible, statistically significant differences in moduli between the patella and the medial/lateral femoral condyles. Typically, femoral cartilage showed higher Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately reproduced the topographical variation in moduli. Additionally, T1, T2, and dGEMRIC revealed topographical differences that were not registered mechanically. The different MRI and mechanical parameters showed poor to excellent linear correlations, up to r = 0.87, at individual test sites. After all specimens were pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N = 77). The results suggest that quantitative MRI can indirectly provide information on the mechanical properties of human knee articular cartilage, as well as the site-dependent variations of these properties. Investigators should consider the topographical variation in MRI parameters when conducting quantitative MRI of cartilage in vivo.     

Advances in musculoskeletal MRI: Technical considerations

The technology of musculoskeletal magnetic resonance imaging (MRI) is advancing at a dramatic rate. MRI is now done at medium and higher field strengths with more specialized surface coils and with more variable pulse sequences and postprocessing techniques than ever before. These innumerable technical advances are advantageous as they lead to an increased signal‐to‐noise ratio and increased variety of soft‐tissue contrast options. However, at the same time they potentially produce more imaging artifacts when compared with past techniques. Substantial technical advances have considerable clinical challenges in musculoskeletal radiology such as postoperative patient imaging, cartilage mapping, and molecular imaging. In this review we consider technical advances in hardware and software of musculoskeletal MRI along with their clinical applications. J. Magn. Reson. Imaging 2012;36:775–787. © 2012 Wiley Periodicals, Inc.     

In vivo evaluation of biomechanical properties in the patellofemoral joint after matrix-associated autologous chondrocyte transplantation by means of quantitative T2 MRI

Purpose

To determine in vivo biomechanical properties of articular cartilage and cartilage repair tissue of the patella, using biochemical MRI by means of quantitative T2 mapping.

Methods

Twenty MR scans were achieved at 3T MRI, using a new 8-channel multi-function coil allowing controlled bending of the knee. Multi-echo spin-echo T2 mapping was prepared in healthy volunteers and in age- and sex-matched patients after matrix-associated autologous chondrocyte transplantation (MACT) of the patella. MRI was performed at 0° and 45° of flexion of the knee after 0 min and after 1 h. A semi-automatic region-of-interest analysis was performed for the whole patella cartilage. To allow stratification with regard to the anatomical (collagen) structure, further subregional analysis was carried out (deep–middle–superficial cartilage layer). Statistical analysis of variance was performed.

Results

During 0° flexion (decompression), full-thickness T2 values showed no significant difference between volunteers (43 ms) and patients (41 ms). Stratification was more pronounced for healthy cartilage compared to cartilage repair tissue. During 45° flexion (compression), full-thickness T2 values within volunteers were significantly increased (54 ms) compared to patients (44 ms) (p < 0.001). Again, stratification was more pronounced in volunteers compared to patients. The volunteer group showed no significant increase in T2 values measured in straight position and in bended position. There was no significant difference between the 0- and the 60-min MRI examination. T2 values in the patient group increased between the 0- and the 60-min examination. However, the increase was only significant in the superior cartilage layer of the straight position (p = 0.021).

Conclusion

During compression (at 45° flexion), healthy patellar cartilage showed a significant increase in T2-values, indicating adaptations of water content and collagen fibril orientation to mechanical load. This could not be observed within the patella cartilage after cartilage repair (MACT) of the patella, most obvious due to a lack of biomechanical adjustment.

Level of evidence

III.     

Postoperative MR evaluation of chondral repair in the knee

Articular cartilage abnormalities of the knee are a cause of significant patient morbidity. Several surgical techniques have been developed to treat these lesions to improve patient symptoms and to delay or prevent the development of osteoarthritis. MRI has been shown to be an accurate non-invasive test for the evaluation of articular cartilage injuries and for evaluating the postoperative knee following chondral repair. As these surgical repair techniques become more commonly performed, is important for radiologists to be familiar with the surgical techniques and the MRI appearance of the postoperative knee including both normal and abnormal findings. In this article, these chondral repair techniques will be reviewed as well those normal and abnormal MRI findings following these surgeries.     

Clinical and MRI considerations in sports-related knee joint cartilage injury and cartilage repair

Cartilage injuries of the knee occur frequently in professional and amateur athletes and can be associated with severe debilitation and morbidity. They are commonly associated with ligament injuries but also may be frequently isolated. Increasing awareness and advances in magnetic resonance imaging (MRI) have led to increasing diagnosis and recognition of these injuries. Articular cartilage is just 2 to 4 mm thick and is avascular, alymphatic, and aneural. It has a limited capacity for healing, and there has been increasing use of cartilage repair techniques to treat these lesions in the active population. Strategies for cartilage repair include marrow stimulation techniques such as microfracture/drilling, osteochondral grafting, and autologous chondrocyte transplants. MRI is an important tool in the diagnosis and grading of cartilage injury and is useful in the follow-up and monitoring of these repair procedures. It is important for radiologists and clinicians to be aware of the capabilities and limitations of MRI in assessing cartilage injury and to be familiar with common postsurgical appearances to facilitate assessment and follow-up in this population. This article reviews the clinical findings and MRI imaging appearances of cartilage injury. The management options are discussed as well as common postsurgical appearances following the various interventions.     

Cartilage imaging: motivation,techniques, current and future significance

Cartilage repair techniques and pharmacological therapies are currently areas of major clinical interest and research, in particular to prevent and treat osteoarthritis. MR imaging-based techniques to visualize cartilage are prerequisites to guide and monitor these therapies. In this review article, standard MR imaging sequences are described, including proton density-weighted fast spin echo, spoiled gradient echo and dual echo steady state sequences. In addition, new sequences that have been developed and are currently being investigated are presented, including driven equilibrium Fourier transform and steady-state free precession-based imaging. Using high-field MR imaging at 3.0-T, visualization of cartilage and the related pathology has been improved. Volumetric quantitative cartilage MR imaging was developed as a tool to monitor the progression of osteoarthritis and to evaluate new pharmacological cartilage protective therapies. The most exciting developments, however, are in the field of cartilage matrix assessment with quantitative dGEMRIC, T2 and T1rho mapping techniques. These techniques aim at detecting cartilage damage at a stage when changes are potentially still reversible, before cartilage tissue is lost. There is currently substantial interest in these techniques from rheumatologists and orthopedists; radiologists therefore need to keep up with these developments.     

Arthroscopic autologous chondrocyte implantation in osteochondral lesions of the talus: mid-term T2-mapping MRI evaluation

Purpose  

Autologous chondrocyte implantation (ACI) in the ankle has become an established procedure to treat osteochondral lesions. However, a non-invasive method able to provide information on the nature of the repair tissue is needed. Recently, MRI T2 mapping was identified as a method capable of qualitatively characterizing articular cartilage. The aim of this study was to evaluate the mid-term results of a series of patients arthroscopically treated by ACI and investigate the nature of the repair tissue by MRI T2 mapping.     

Non-invasive MRI assessment of the articular cartilage in clinical studies and experimental settings

Attrition and eventual loss of articular cartilage are important elements in the pathophysiology of osteoarthritis (OA). Preventing the breakdown of cartilage is believed to be critical to preserve the functional integrity of a joint. Chondral injuries are also common in the knee joint, and many patients benefit from cartilage repair. Magnetic resonance imaging (MRI) and advanced digital post-processing techniques have opened possibilities for in vivo analysis of cartilage morphology, structure, and function in healthy and diseased knee joints. Techniques of semi-quantitative scoring of human knee cartilage pathology and quantitative assessment of human cartilage have been developed. Cartilage thickness and volume have been quantified in humans as well as in small animals. MRI detected cartilage loss has been shown to be more sensitive than radiographs detecting joint space narrowing. It is possible to longitudinally study knee cartilage morphology with enough accuracy to follow the disease-caused changes and also evaluate the therapeutic effects of chondro-protective drugs. There are also several MRI methods that may allow evaluation of the glycosaminoglycan matrix or collagen network of articular cartilage, and may be more sensitive for the detection of early changes. The clinical relevance of these methods is being validated. With the development of new therapies for OA and cartilage injury, MR images will play an important role in the diagnosis, staging, and evaluation of the effectiveness of these therapies.     

An improved coverage and spatial resolution—using dual injection dynamic contrast‐enhanced (ICE‐DICE) MRI: A novel dynamic contrast‐enhanced technique for cerebral tumors

A new dual temporal resolution‐based, high spatial resolution, pharmacokinetic parametric mapping method is described ‐ improved coverage and spatial resolution using dual injection dynamic contrast‐enhanced (ICE‐DICE) MRI. In a dual‐bolus dynamic contrast‐enhanced‐MRI acquisition protocol, a high temporal resolution prebolus is followed by a high spatial resolution main bolus to allow high spatial resolution parametric mapping for cerebral tumors. The measured plasma concentration curves from the dual‐bolus data were used to reconstruct a high temporal resolution arterial input function. The new method reduces errors resulting from uncertainty in the temporal alignment of the arterial input function, tissue response function, and sampling grid. The technique provides high spatial resolution 3D pharmacokinetic maps (voxel size 1.0 × 1.0 × 2.0 mm³) with whole brain coverage and greater parameter accuracy than that was possible with the conventional single temporal resolution methods. High spatial resolution imaging of brain lesions is highly desirable for small lesions and to support investigation of heterogeneity within pathological tissue and peripheral invasion at the interface between diseased and normal brain. The new method has the potential to be used to improve dynamic contrast‐enhanced‐MRI techniques in general. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Quantitative MRI in the evaluation of articular cartilage health: reproducibility and variability with a focus on T2 mapping

Purpose

Early diagnosis of cartilage degeneration and longitudinal tracking of cartilage health including repair following surgical intervention would benefit from the ability to detect and monitor changes of the articular cartilage non-invasively and before gross morphological alterations appear.

Methods

Quantitative MR imaging has shown promising results with various imaging biomarkers such as T2 mapping, T1 rho and dGEMRIC demonstrating sensitivity in the detection of biochemical alterations within tissues of interest. However, acquiring accurate and clinically valuable quantitative data has proven challenging, and the reproducibility of the quantitative mapping technique and its values are essential. Although T2 mapping has been the focus in this discussion, all quantitative mapping techniques are subject to the same issues including variability in the imaging protocol, unloading and exercise, analysis, scanner and coil, calculation methods, and segmentation and registration concerns.

Results

The causes for variability between time points longitudinally in a patient, among patients, and among centres need to be understood further and the issues addressed.

Conclusions

The potential clinical applications of quantitative mapping are vast, but, before the clinical community can take full advantage of this tool, it must be automated, standardized, validated, and have proven reproducibility prior to its implementation into the standard clinical care routine.