Ravinder R. Regatte

Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST).

Glycosaminogycans (GAGs) are involved in numerous vital functions in the human body. Mapping the GAG concentration in vivo is desirable for the diagnosis and monitoring of a number of diseases such as osteoarthritis, which affects millions of individuals. GAG loss in cartilage is typically an initiating event in osteoarthritis. Another widespread pathology related to GAG is intervertebral disk degeneration. Currently existing techniques for GAG monitoring, such as delayed gadolinium-enhanced MRI contrast (dGEMRIC), T1ρ, and 23Na MRI, have some practical limitations. We show that by exploiting the exchangeable protons of GAG one may directly measure the localized GAG concentration in vivo with high sensitivity and therefore obtain a powerful diagnostic MRI method.

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

To quantify the spin‐lattice relaxation time in the rotating frame (T1ρ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1ρ with OA disease progression and compare it with the transverse relaxation time (T2).

Ultra‐high‐field MRI of the musculoskeletal system at 7.0T

High‐field (3T) and ultra‐high‐field (UHF, 7T and above) systems are increasingly being used to explore potential musculoskeletal applications because they provide a high intrinsic signal‐to‐noise ratio (SNR), potentially higher resolution (spatial and temporal), and improved contrast. However, imaging at 7T and above presents certain challenges, such as homogeneous radiofrequency (RF) coil design, increased chemical shift artifacts, susceptibility artifacts, RF energy deposition, and changes in relaxation times compared to more typical clinical scanners (1.5 and 3T). Despite these issues, MRI at 7T likely will provide some excellent opportunities for high‐resolution morphologic imaging and forays into functional imaging of musculoskeletal systems. In this review we address some of these issues and also demonstrate the feasibility of acquiring high‐resolution in vivo images of the musculoskeletal system in healthy human volunteers at 7.0T. J. Magn. Reson. Imaging 2007.

Biomedical applications of sodium MRI in vivo.

In this article we present an up‐to‐date overview of the potential biomedical applications of sodium magnetic resonance imaging (MRI) in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle, and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: 1) the role of sodium in biological tissues, 2) a short review on sodium magnetic resonance, and 3) a review of some studies on sodium MRI on different organs/diseases to date.J. Magn. Reson. Imaging 2013;38:511–529.

Rapid Isotropic 3D-Sodium MRI of the Knee Joint In-vivo at 7T

To demonstrate the feasibility of acquiring high‐resolution, isotropic 3D‐sodium magnetic resonance (MR) images of the whole knee joint in vivo at ultrahigh field strength (7.0T) via a 3D‐radial acquisition with ultrashort echo times and clinically acceptable acquisition times.

Isolating chemical exchange saturation transfer contrast from magnetization transfer asymmetry under two-frequency rf irradiation.

Chemical exchange saturation transfer (CEST), arising from mobile groups, and magnetization transfer (MT) contrast arising from immobile protons, have enjoyed wide popularity recently in MRI applications. It is often difficult to separate genuine CEST signatures from MT effects, which are asymmetric with respect to the water resonance. A two-pool model for magnetization transfer (MT) is established based on Provotorovs theory of saturation, and then extended to the situation of simultaneous two-frequency rf irradiation. Numerical simulations and experimental results demonstrate that two-frequency rf irradiation can flatten out MT asymmetry when both frequency components lie within the spectrum of an MT pool. Based on this result, we propose a strategy to isolate chemical exchange saturation transfer (CEST) contrast from MT asymmetry contrast by using the two-frequency rf irradiation technique.

Quantitative magnetic resonance imaging evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis.

OBJECTIVE To evaluate the relationships between both quantitative and semiquantitative assessments of the degree of knee synovitis on 3T magnetic resonance imaging (MRI) and the severity of knee osteoarthritis (OA) on radiography. METHODS Fifty-eight patients with knee OA underwent nonfluoroscopic fixed-flexion knee radiography. In addition, dynamic contrast-enhanced 3T MRI of the knees was performed, before and after gadolinium administration, to quantify synovial membrane volume (SV) as a measure of synovial proliferation (expressed as the quantitative SV), and semiquantitative measures of synovitis were also applied using both contrast-enhanced and unenhanced images. Two radiologists scored the knee radiographs using the Osteoarthritis Research Society International atlas; interreader agreement was assessed using kappa statistics and concordance correlation coefficients. Multiple linear and logistic regression analyses were used to assess associations among variables, while controlling for the effects of age, body mass index, sex, and meniscal extrusion. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for measures of disease activity. RESULTS The Kellgren/Lawrence (K/L) grade of radiographic knee OA severity (β=0.78), the diseased compartment joint space width (dcJSW) (β=-0.22), and the diseased compartment joint space narrowing (dcJSN) score (β=0.53) were each significantly associated with the quantitative SV (P=0.0001, P=0.0003, and P=0.0001, respectively). Furthermore, the quantitative SV strongly correlated with the total volume of subchondral bone marrow lesions (BMLs) (β=0.22, P=0.0003). The K/L grade, dcJSW, and dcJSN score were each significantly associated with the semiquantitative Boston Leeds Osteoarthritis Knee Score (BLOKS) for the extent of infrapatellar synovitis (OR 9.05 [95% CI 1.94, 42.3] for K/L grade; OR 0.75 [95% CI 0.54, 1.03] for dcJSW; and OR 2.22 [95% CI 1.15, 4.31] for dcJSN score) and extent of joint effusion (OR 5.75 [95% CI 1.23, 26.8] for K/L grade; OR 0.70 [95% CI 0.50, 0.98] for dcJSW; and OR 1.96 [95% CI 1.02, 3.74] for dcJSN score). In addition, the semiquantitative synovitis grade on contrast-enhanced MRI was significantly associated with the K/L grade (β=0.036, P=0.0040) and dcJSN score (β=0.015, P=0.0266), and also significantly associated with the BLOKS synovitis score. CONCLUSION Synovitis is a characteristic feature of advancing knee OA and is significantly associated with the K/L grade, JSW, JSN score, and total volume of BMLs on radiographs. Furthermore, BLOKS scoring of synovitis on unenhanced MRI is associated with measurements of synovitis on contrast-enhanced MRI.

Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis.

Osteoarthritis (OA), a leading cause of disability, affects 27 million people in the United States and its prevalence is rising along with the rise in obesity. So far, biomechanical or behavioral interventions as well as attempts to develop disease-modifying OA drugs have been unsuccessful. This may be partly due to antiquated imaging outcome measures such as radiography, which are still endorsed by regulatory agencies such as the United States Food and Drug Administration (FDA) for use in clinical trials. Morphological magnetic resonance imaging (MRI) allows unparalleled multi-feature assessment of the OA joint. Furthermore, advanced MRI techniques also enable evaluation of the biochemical or ultrastructural composition of articular cartilage relevant to OA research. These compositional MRI techniques have the potential to supplement clinical MRI sequences in identifying cartilage degeneration at an earlier stage than is possible today using morphologic sequences only. The purpose of this narrative review is to describe compositional MRI techniques for cartilage evaluation, which include T2 mapping, T2* Mapping, T1 rho, dGEMRIC, gagCEST, sodium imaging and diffusion weighted imaging (DWI). We also reviewed relevant clinical studies that have utilized these techniques for the study of OA. The different techniques are complementary. Some focus on isotropy or the collagen network (e.g., T2 mapping) and others are more specific in regard to tissue composition, e.g., gagCEST or dGEMRIC that convey information on the GAG concentration. The application and feasibility of these techniques is also discussed, as they will play an important role in implementation in larger clinical trials and eventually clinical practice.

Sodium inversion recovery MRI of the knee joint in vivo at 7T.

The loss of proteoglycans (PG) in the articular cartilage is an early signature of osteoarthritis (OA). The ensuing changes in the fixed charge density in the cartilage can be directly linked to sodium concentration via charge balance. Sodium ions in the knee joint appear in two pools: in the synovial fluids or joint effusion where the ions are in free motion and bound within the cartilage tissue where the Na(+) ions have a restricted motion. The ions in these two compartments have therefore different T₁ and T₂ relaxation times. The purpose of this study is to demonstrate the feasibility of a fluid-suppressed 3D ultrashort TE radial sodium sequence by implementing an inversion recovery (IR) preparation of the magnetization at 7T. This method could allow a more accurate and more sensitive quantification of loss of PG in patients with OA. It is shown that adiabatic pulses offer significantly improved performance in terms of robustness to B₁ and B₀ inhomogeneities when compared to the hard pulse sequence. Power deposition considerations further pose a limit to the RF inversion power, and we demonstrate in simulations and experiments how a practical compromise can be struck between clean suppression of fluid signals and power deposition levels. Two IR sequences with different types of inversion pulses (a rectangular pulse and an adiabatic pulse) were tested on a liquid phantom, ex vivo on a human knee cadaver and then in vivo on five healthy volunteers, with a (Nyquist) resolution of ∼3.6 mm and a signal-to-noise ratio of ∼30 in cartilage without IR and ∼20 with IR. Due to specific absorption rate limitations, the total acquisition time was ∼17 min for the 3D radial sequence without inversion or with the rectangular IR, and 24:30 min for the adiabatic IR sequence. It is shown that the adiabatic IR sequence generates a more uniform fluid suppression over the whole sample than the rectangular IR sequence.

Assessment of glycosaminoglycan concentration changes in the intervertebral disc via chemical exchange saturation transfer.

In this study, it is shown that the chemical exchange saturation transfer (CEST) method for hydroxyl protons can be used to detect changes in glycosaminoglycan (GAG) concentration in the intervertebral disc. The method, termed gagCEST, was demonstrated ex vivo by correlating the CEST effect with the fixed charge density (FCD) of the nucleus pulposus (NP), as well as by correlating tissue CEST images with their corresponding 23Na images. Incubation of five NP samples with trypsin produced samples with varying GAG content (n = 19). A good correlation was found between the –OH CEST effect and FCD, as well as with the N‐acetyl signal amplitude. gagCEST images in vitro further illustrated the amount of detail obtainable from this contrast mechanism when compared with conventional imaging. The large concentration of GAG and the relatively long T1 of water in NP make the method sensitive, in particular, for the assessment of GAG depletion in this tissue. It is the loss of GAG in NP that indicates the early stage of disc degeneration. Copyright