Proteoglycan‐induced changes in <i>T</i><sub>1ρ</sub>‐relaxation of articular cartilage at 4T

Akella, Sarma V.S.; Regatte, Ravinder R.; Gougoutas, Alexander J.; Borthakur, Arijitt; Shapiro, Erik M.; Kneeland, J. Bruce; Leigh, John S.; Reddy, Ravinder

doi:10.1002/mrm.1208

Cited by 358 publications

(366 citation statements)

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“…However, except for a constant shift, there were no significant changes observed in the T 1r dispersion curve with varying levels of GAG depletion by trypsin (25). Discrepancy between these results may be due to the measurement of global (spectroscopic) vs (imaging) regional T 1r and difference in static field strength.…”

Section: T 1r Dispersion In Cartilagementioning

confidence: 79%

“…Prominent in these are: proton-based methods such as T 2 relaxation mapping (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), delayed gadoliniumenhanced magnetic resonance imaging contrast (dGEM-RIC) (21,22), T 1r relaxation mapping (23)(24)(25)(26) and the direct MRI of sodium (27)(28)(29)(30). T 2 is predominantly affected by changes in collagen content and to a smaller extent in PG in the tissue.…”

Section: Osteoarthritismentioning

confidence: 99%

“…In an elegant study on bovine articular cartilage patellae, sequential trypsin-induced PG depletion was performed (25). Proton T 1r maps were generated at varying B 1 fields at 4 T using a home-built RF coil.…”

Section: Experimental T 1r Studiesmentioning

confidence: 99%

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Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

et al. 2006

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In this article, both sodium magnetic resonance (MR) and T 1r relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T 1r , a brief description of (i) principles of measuring T 1r relaxation, (ii) pulse sequences for computing T 1r relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T 1r in biological tissues and (v) effects of exchange and dipolar interaction on T 1r dispersion are discussed. Correlation of T 1r relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokineinduced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T 1r data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T 1r relaxation mapping of cartilage and future directions is also discussed. Copyright # 2006 John Wiley & Sons, Ltd. KEYWORDS: cartilage; arthritis; spin-lock; T1rho; sodium; MRI OSTEOARTHRITIS Osteoarthritis (OA) affects more than half of the population above the age of 65 (1,2) and has a significant negative impact on the quality of life of elderly individuals (3). The economic costs in the USA from OA have been estimated to be more than 1% of the gross domestic product (4). OA is now increasingly viewed as a metabolically active joint disorder of diverse etiologies. The biochemistry of the disease is characterized by the following changes in cartilage: reduced proteoglycan (PG) concentration, possible changes in the size of collagen fibril and aggregation of PG, increased water content and increased rate of synthesis and degradation of matrix macromolecules. The earliest changes in the cartilage due to OA result in a partial breakdown in the proteoglyc...

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Section: T 1r Dispersion In Cartilagementioning

confidence: 79%

Section: Osteoarthritismentioning

confidence: 99%

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Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

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“…Since PG loss is an initiating event of OA, the ability to noninvasively quantitate PG changes may be useful for making an early diagnosis, monitoring response to therapy, assessing the efficacy of cartilage repair, and conducting longitudinal follow-up studies. Different magnetic resonance imaging (MRI) techniques have been proposed to quantify early biochemical changes in cartilage, particularly PG changes (1)(2)(3)(4)(5)(6)(7)(8). Although MRI can detect cartilage fibrillation more accurately than other diagnostic techniques, conventional MRI techniques are insensitive in detecting early changes in OA.…”

mentioning

confidence: 99%

“…Recent in vitro and in vivo studies on cartilage have demonstrated that the T 1 is sensitive to changes in the PG content of cartilage (7,8,21). In a study of bovine cartilage it was shown that the T 1 relaxation rate changes linearly with changes in the PG content of cartilage (6). It was also reported that spin-lock MRI (22) eliminates residual dipolar interaction (RDI) in cartilage as long as the amplitude of the spin-lock pulse is greater than the RDI.…”

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T_1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T_1ρ with T₂

Regatte

Akella

Lonner

et al. 2006

Magnetic Resonance Imaging

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Purpose:To quantify the spin-lattice relaxation time in the rotating frame (T 1 ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T 1 with OA disease progression and compare it with the transverse relaxation time (T 2 ). Materials and Methods:Human cartilage specimens were obtained from consenting patients (N ϭ 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T 2 -and T 1 -weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed.Results: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T 2 and T 1 ) compared to healthy cartilage tissue. In various grades of OA specimens, the T 1 relaxation times varied from 62 Ϯ 5 msec to 100 Ϯ 8 msec (mean Ϯ SEM) depending on the degree of cartilage degeneration. However, T 2 relaxation times varied only from 32 Ϯ 2 msec to 45 Ϯ 4 msec (mean Ϯ SEM) on the same cartilage specimens. The increase in T 2 and T 1 in various clinical grades of OA specimens were ϳ5-50% and 30 -120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. Conclusion:Preliminary results from a limited number of knee specimens (N ϭ 8) suggest that T 1 relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T 1 has a higher dynamic range (Ͼ100%) for detecting early pathology compared to T 2 . This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T 2 . Because of these advantages, T 1 relaxation mapping may be useful for evaluating early OA therapy.

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Biomaterials to Mimic and Heal Connective Tissues

2019

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Connective tissue is one of the four major types of animal tissue and plays essential roles throughout the human body. Genetic factors, aging, and trauma all contribute to connective tissue dysfunction and motivate the need for strategies to promote healing and regeneration. The goal of this Review is to link a fundamental understanding of connective tissues and their multiscale properties to better inform the design and translation of novel biomaterials to promote their regeneration. We discuss major clinical problems in adipose tissue, cartilage, dermis, and tendon that inspire the need to replace native connective tissue with biomaterials. We then detail multiscale structure-function relationships in native soft connective tissues that may be used to guide material design. Several biomaterials strategies to improve healing of these tissues that incorporate biologics and are biologic-free are reviewed. Finally, we highlight important guidance documents and standards (ASTM, FDA, EMA) that are important to consider for translating new biomaterials into clinical practice.

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Proteoglycan‐induced changes in T_1ρ‐relaxation of articular cartilage at 4T

Cited by 358 publications

References 33 publications

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

T_1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T_1ρ with T₂

Biomaterials to Mimic and Heal Connective Tissues

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Proteoglycan‐induced changes in T1ρ‐relaxation of articular cartilage at 4T

Cited by 358 publications

References 33 publications

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

T1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T1ρ with T2

Biomaterials to Mimic and Heal Connective Tissues

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Proteoglycan‐induced changes in T_1ρ‐relaxation of articular cartilage at 4T

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

T_1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T_1ρ with T₂