MRI rotating frame relaxation measurements for articular cartilage assessment

In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T_1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T_1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T₂ and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48 h in 10 bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48 h. Relaxation times measured at 48 h were longer than those measured at 0 h in both groups. The changes in T₂ and MT relaxation times after 48 h were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T_1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T_1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T₂ and MT. Since adiabatic T_1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T_1ρ methods, adiabatic T_1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings.     

Evaluation of the role of magnetization transfer imaging in prostate: a preliminary study

Results of the preliminary study on the evaluation of the role of magnetization transfer imaging (MTI) of prostate in men who had raised prostate-specific antigen (PSA) (>4 ng/ml) or abnormal digital rectal examination (DRE) are reported. MT ratio (MTR) was calculated for 20 patients from the hyper- (normal) and hypo-intense regions (area suspicious of malignancy as seen on T2-weighted MRI) of the peripheral zone (PZ) and the central gland (CG) at 1.5 T. In addition, MTR was calculated for three healthy controls. Mean MTR was also calculated for the whole of the PZ (including hyper- and hypo-intense area) in all patients. Out of 20 patients, biopsy revealed malignancy in 12 patients. Mean MTR value (8.29+/-3.49) for the whole of the PZ of patients who were positive for malignancy on biopsy was statically higher than that observed for patients who were negative for malignancy (6.18+/-3.15). The mean MTR for the whole of the PZ of controls was 6.18+/-1.63 and is similar to that of patients who were negative for malignancy. Furthermore, for patients who showed hyper- (normal portion) and hypo-intense (region suspicious of malignancy) regions of the PZ, the MTR was statistically significantly different. These preliminary results reveal the potential role of MT imaging in the evaluation of prostate cancer.     

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T₁-weighted, T₂-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T₁ and T₂ weighted images were collected in UUO mice on day 0 (~ 3 h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p < 0.05) changes in thickness of cortex and outer medulla, and regional changes in T₂ signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical–medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression.     

Generalized equation for describing the magnetization in spoiled gradient-echo imaging

The purpose of this study was to demonstrate a generalized equation for describing the magnetization in spoiled gradient-echo (SPGR) imaging in which the in-pulse relaxation and magnetization transfer (MT) effects are taken into account. First, the time-dependent Bloch equations for the two-pool exchange model with MT effect were reduced to an inhomogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation. Second, the equations describing the magnetization before and after the radiofrequency (RF) pulse were derived based on the above solution for the RF-pulse excitation and evolution phases. Finally, a generalized equation describing the steady-state magnetization was derived. The validity of this equation was investigated by comparing with the transverse magnetization obtained by the regular Ernst equation and analytical solution in which the in-pulse transverse relaxation is considered. When the same assumption was made in our method, there were good agreements between them, indicating the validity of our method. The in-pulse transverse and longitudinal relaxations decreased the transverse magnetization compared to the case in which these effects were neglected, whereas MT increased it. In conclusion, we derived a generalized equation for describing the magnetization in SPGR imaging. This equation will provide a suitable basis for understanding the signal intensity in SPGR imaging and/or T₁ measurement using an SPGR sequence in cases in which the effect of in-pulse relaxation and/or MT cannot be neglected.     

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spinspin relaxation time (T₂), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T₂ value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between “free” and “bound” water protons as measured by MTC imaging is at least partially responsible for the elevation in T₂ values observed during ischemia, and may accompany breakdown of cellular structure.     

Diffusion tensor imaging of native and degenerated human articular cartilage

Diffusion tensor imaging (DTI) is potentially sensitive to collagen degeneration in cartilage. In this study, DTI was measured on human cartilage samples with interventions of trypsin and collagenase. The measured preferred diffusion direction was consistent with the zonal structure of collagen network. The glycosaminoglycan concentration decreased and apparent diffusion coefficient increased with both interventions. The fractional anisotropy (FA) was not affected by trypsin and showed a slight increase with combined trypsin and collagenase intervention. DTI in cartilage is technically challenging due to the low FA and the almost undetectable change with collagen disruption seen here.     

Inverse polarization transfer for detecting in vivo 13C magnetization transfer effect of specific enzyme reactions in 1H spectra

The wide chemical shift dispersion and long T(1) of (13)C have allowed determination of in vivo magnetization transfer effects caused by aspartate aminotransferase and lactate dehydrogenase reactions using (13)C magnetic resonance spectroscopy. In this report, we demonstrate that these effects can be observed in the proton spectra by transferring the equilibrium magnetization of (13)C via the one-bond scalar coupling between (13)C and (1)H using an inverse insensitive nuclei enhanced by polarization transfer-based heteronuclear polarization transfer method. This inverse method allows a combination of the advantages of the long (13)C T(1) for maximum magnetization transfer and the high sensitivity of proton detection. The feasibility of this in vivo inverse polarization transfer approach was evaluated for detecting the (13)C magnetization transfer effect of aspartate aminotransferase and lactate dehydrogenase reactions from a 72.5-microl voxel in the rat brain at 11.7 T.     

Quantitative assessment of mobile protein levels in human knee synovial fluid: feasibility of chemical exchange saturation transfer (proteinCEST) MRI of osteoarthritis

Purpose

To establish the feasibility of chemical exchange saturation transfer (proteinCEST) MRI in the differentiation of osteoarthritis (OA) knee joints from non-OA joints by detecting mobile protein and peptide levels in synovial fluid by determining their relative distribution.

Materials and Methods

A total of 25 knees in 11 men and 12 women with knee injuries were imaged using whole knee joint proteinCEST MRI sequence at 3 T. The joint synovial fluid was segmented and the asymmetric magnetization transfer ratio at 3.5 ppm MTR_asym (3.5 ppm) was calculated to assess protein content in the synovial fluid. The 85th percentile of synovial fluid MTR_asym (3.5 ppm) distribution profile was compared using the independent Student's t test. The diagnostic performance of the 85th percentile of synovial fluid MTR_asym (3.5 ppm) in differentiating OA and non-OA knee joints was evaluated.

Results

The 85th percentile of synovial fluid MTR_asym (3.5 ppm) in knee joints with OA was 8.6%±3.4% and significantly higher than that in the knee joints without OA (6.3%±1.4%, P<.05). A knee joint with an 85th percentile of synovial fluid MTR_asym (3.5 ppm) greater than 7.7% was considered to be an OA knee joint. With the threshold, the sensitivity, specificity and overall accuracy for differentiating knee joints with OA from the joints without OA were 54% (7/13), 92% (11/12) and 72% (18/25), respectively.

Conclusion

proteinCEST MRI appears feasible as a quantitative methodology to determine mobile protein levels in synovial fluid and identify patterns characteristic for OA disease.     

Macroscopic tumor volume of malignant glioma determined by contrast-enhanced magnetic resonance imaging with and without magnetization transfer contrast

The purposes of this study were to compare the conspicuity and lesion volume of contrast-enhancing macroscopic malignant glioma determined by postcontrast magnetic resonance (MR) imaging with and without magnetization transfer (MT) saturation, and to discuss possible implications for radiotherapy planning. Nineteen patients (age 24–60 years) with histologically proven malignant glioma were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight), the lesions were imaged with an MT-weighted FLASH (fast, low-angle shot) pulse sequence and with a conventional T₁-weighted spin-echo (SE) sequence without MT saturation. The mean tumor volumes of gliomas measured on MT-weighted FLASH images were significantly (p < .01) larger than those obtained from T₁-weighted SE images (45 ± 15 cm³ vs. 33 ± 10 cm³). The mean contrast-to-noise ratio of enhancing lesions on MT-weighted FLASH was 48 ± 14 compared with 30 ± 14 on SE images, representing a significant (p < .01) improvement. We conclude that the volume of contrast enhancement of malignant glioma identified on MT-weighted FLASH images represents the area of disrupted blood-brain barrier. If this volume of subtle contrast enhancement is caused by tumor infiltration and represents the boost target volume for stereotactic radiosurgery or brachytherapy, MT-weighted FLASH images would be better than T₁-weighted SE images to define these volumes. These improved delineation of areas at highest risk for recurrence following radiation therapy should enhance the efficacy of treatment planning for high-boost therapy.     

Dynamics of paramagnetic agents by off-resonance rotating frame technique in the presence of magnetization transfer effect

The simple method for measuring the rotational correlation time of paramagnetic ion chelates via off-resonance rotating frame technique is challenged in vivo by the magnetization transfer effect. A theoretical model for the spin relaxation of water protons in the presence of paramagnetic ion chelates and magnetization transfer effect is described. This model considers the competitive relaxations of water protons by the paramagnetic relaxation pathway and the magnetization transfer pathway. The influence of magnetization transfer on the total residual z-magnetization has been quantitatively evaluated in the context of the magnetization map and various difference magnetization profiles for the macromolecule conjugated Gd-DTPA in cross-linked protein gels. The numerical simulations and experimental validations confirm that the rotational correlation time for the paramagnetic ion chelates can be measured even in the presence of strong magnetization transfer. This spin relaxation model also provides novel approaches to enhance the detection sensitivity for paramagnetic labeling by suppressing the spin relaxations caused by the magnetization transfer. The inclusion of the magnetization transfer effect allows us to use the magnetization map as a simulation tool to design efficient paramagnetic labeling targeting at specific tissues, to design experiments running at low RF power depositions, and to optimize the sensitivity for detecting paramagnetic labeling. Thus, the presented method will be a very useful tool for the in vivo applications such as molecular imaging via paramagnetic labeling.     

Relayed (13)C magnetization transfer: detection of malate dehydrogenase reaction in vivo

Malate dehydrogenase catalyzes rapid interconversion between dilute metabolites oxaloacetate and malate. Both oxaloacetate and malate are below the detection threshold of in vivo MRS. Oxaloacetate is also in rapid exchange with aspartate catalyzed by aspartate aminotransferase, the latter metabolite is observable in vivo using (13)C MRS. We hypothesized that the rapid turnover of oxaloacetate can effectively relay perturbation of magnetization between malate and aspartate. Here, we report indirect observation of the malate dehydrogenase reaction by saturating malate C2 resonance at 71.2 ppm and detecting a reduced aspartate C2 signal at 53.2 ppm due to relayed magnetization transfer via oxaloacetate C2 at 201.3 ppm. Using this strategy the rate of the cerebral malate dehydrogenase reaction was determined to be 9+/-2 micromol/g wet weight/min (means+/-SD, n=5) at 11.7 Tesla in anesthetized adult rats infused with [1,6-(13)C(2)]glucose.     

Physiological assessment of in vivo human knee articular cartilage using sodium MR imaging at 1.5 T

Osteoarthritis is a common joint disorder that is most prevalent in the knee joint. Knee osteoarthritis (OA) can be characterized by the gradual loss of articular cartilage (AC). Formation of lesion, fissures and cracks on the cartilage surface has been associated with degenerative AC and can be measured by morphological assessment. In addition, loss of proteoglycan from extracellular matrix of the AC can be measured at early stage of cartilage degradation by physiological assessment. In this case, a biochemical phenomenon of cartilage is used to assess the changes at early degeneration of AC. In this paper, a method to measure local sodium concentration in AC due to proteoglycan has been investigated. A clinical 1.5-T magnetic resonance imaging (MRI) with multinuclear spectroscopic facility is used to acquire sodium images and quantify local sodium content of AC. An optimised 3D gradient-echo sequence with low echo time has been used for MR scan. The estimated sodium concentration in AC region from four different data sets is found to be ~ 225 ± 19 mmol/l, which matches the values that has been reported for the normal AC. This study shows that sodium images acquired at clinical 1.5-T MRI system can generate an adequate quantitative data that enable the estimation of sodium concentration in AC. We conclude that this method is potentially suitable for non-invasive physiological (sodium content) measurement of articular cartilage.     

Magnetization transfer contrast (MTC) in FLASH MR imaging

Magnetization transfer between bound and free protons was used as a source of contrast in high speed MR imaging using the FLASH technique. Contrast in FLASH MR images was found to depend upon the reduced magnetization and the spin lattice relaxation rate of free protons in the presence of bound proton radio-frequency saturation. MTC FLASH imaging was thus used to estimate the variation with saturation frequency of free proton spin-lattice relaxation during magnetization transfer.     

Assessment of the patellofemoral cartilage: Correlation of knee pain score with magnetic resonance cartilage grading and magnetization transfer ratio asymmetry of glycosaminoglycan chemical exchange saturation transfer

PurposeBiochemical imaging of glycosaminoglycan chemical exchange saturation transfer (gagCEST) could predict the depletion of glycosaminoglycans (GAG) in early osteoarthritis. The purpose of this study was to evaluate the relationship between the magnetization transfer ratio asymmetry (MTR_asym) of gagCEST images and visual analog scale (VAS) pain scores in the knee joint.Materials and methodsThis retrospective study was approved by the institutional review board. A phantom study was performed using hyaluronic acid to validate the MTR_asym values of gagCEST images. Knee magnetic resonance (MR) images of 22 patients (male, 9; female, 13; mean age, 50.3 years; age range; 25–79 years) with knee pain were included in this study. The MR imaging (MRI) protocol involved standard knee MRI as well as gagCEST imaging, which allowed region-of-interest analyses of the patellar facet and femoral trochlea. The MTR_asym at 1.0 ppm was calculated at each region. The cartilages of the patellar facets and femoral trochlea were graded according to the Outerbridge classification system. Data regarding the VAS scores of knee pain were collected from the electronic medical records of the patients. Statistical analysis was performed using Spearman's correlation.ResultsThe results of the phantom study revealed excellent correlation between the MTR_asym values and the concentration of GAGs (r = 0.961; p = 0.003). The cartilage grades on the MR images showed significant negative correlation with the MTR_asym values in the patellar facet and femoral trochlea (r = −0.460; p = 0.031 and r = −0.543; p = 0.009, respectively). The VAS pain scores showed significant negative correlation with the MTR_asym values in the patellar facet and femoral trochlea (r = −0.435; p = 0.043 and r = −0.671; p = 0.001, respectively).ConclusionThe pain scores were associated with the morphological and biochemical changes in articular cartilages visualized on knee MR images. The biochemical changes, visualized in terms of the MTR_asym values of the gagCEST images, exhibited greater correlation with the pain scores than the morphological changes visualized on conventional MR images; these results provide evidence supporting the theory regarding the association of patellofemoral osteoarthritis with knee pain scores.     

Damages to the extracellular matrix in articular cartilage due to cryopreservation by microscopic magnetic resonance imaging and biochemistry

To investigate the damages to the extracellular matrix in articular cartilage due to cryopreservation, the depth-dependent concentration profiles of glycosaminoglycans (GAGs) in 34 cartilage specimens from canine humeral heads were imaged at 13-μm pixel resolution using the in vitro version of the dGEMRIC protocol in microscopic MRI (μMRI). In addition, a biochemical assay was used to determine the GAG loss from the tissue to the solution where the tissue was immersed. For specimens that had been frozen at −20°C or −80°C without any cryoprotectant, a significant loss of GAG (as high as 56.5%) was found in cartilage, dependent upon the structural zones of the tissue and the conditions of cryopreservation. The cryoprotective abilities of dimethyl sulfoxide (DMSO) as a function of its concentration in saline and storage temperature were also investigated. A 30% DMSO concentration was sufficient in preventing the reduction of GAG in the tissue at the −20°C storage temperature, but a 50% concentration of DMSO was necessary for the −80°C cryopreservation. These imaging results were verified by the biochemical analysis.     

Reproducibility of the quantitative assessment of cartilage morphology and trabecular bone structure with magnetic resonance imaging at 7 T

To assess the reproducibility of quantitative measurements of cartilage morphology and trabecular bone structure of the knee at 7 T, high-resolution sagittal spoiled gradient-echo images and high-resolution axial fully refocused steady-state free-precession (SSFP) images from six healthy volunteers were acquired with a 7-T scanner. The subjects were repositioned between repeated scans to test the reproducibility of the measurements. The reproducibility of each measurement was evaluated using the coefficient(s) of variation (CV). The computed CV were 1.13% and 1.55% for cartilage thickness and cartilage volume, respectively, and were 2.86%, 1.07%, 2.27% and 3.30% for apparent bone volume over total volume fraction (app.BV/TV), apparent trabecular number (app.Tb.N), apparent trabecular separation (app.Tb.Sp) and apparent trabecular thickness (app.Tb.Th), respectively. The results demonstrate that quantitative assessment of cartilage morphology and trabecular bone structure is reproducible at 7 T and motivates future musculoskeletal applications seeking the high-field strength's superior signal-to-noise ratio.     

Quantitative analysis of magnetization reversal in patterned strip wire by magnetic force microscopy

Magnetic force microscopy (MFM) was used to investigate the magnetization reversal process in a patterned strip wire of permalloy thin film. The magnitude of the phase-shift of tapping mode MFM changed with the varying interactive magnetic force between the magnetic tip and the sample. By analyzing the change in values of the phase-shift, the behaviors of magnetization reversal of different local regions in a patterned strip wire can be quantitatively analyzed. The intensity of the phase-shift in the wider end is stronger than that in the narrower one. In contrast, due to a strong anisotropic effect, the coercive force in the narrower end (9 Oe) is larger than that in the wider one (8 Oe). Therefore, the H_c in the neck section could become strongly affected by the competition of the head-to-tail magnetic configurations in the two parts of the strip wire, and this results in a small H_c in the neck section. In addition, in a simple neck shape connection in a strip NiFe wire, a single domain configuration can be easily changed to a two single domain magnetic configuration.     

Comparison of quantitative imaging of cartilage for osteoarthritis: T2, T1ρ, dGEMRIC and contrast-enhanced computed tomography

Evaluation of glycosaminoglycan (GAG) concentration in articular cartilage is of particular interest to the study of degenerative joint diseases such as osteoarthritis (OA). Noninvasive imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) have demonstrated the potential to assess biochemical markers of cartilage integrity such as GAG content; however, many imaging techniques are available and the optimization of particular techniques in the diagnosis of joint disease remains an active area of research. In order to highlight the differences between these various approaches, this work compares MRI (T1, T2 and T1ρ) and contrast-enhanced CT in human articular cartilage, in both the presence and absence of gadolinium-based contrast agent. Pre- and postcontrast T2 values were found to be similar on a regional level and correlated with each other. As expected, T1 values were shortened significantly on both a global and a spatial basis in the presence of gadolinium (Gd); similar results were found for T1ρ. T2 values were found to correlate mildly with postcontrast T1, T1(Gd) and with precontrast T1ρ values. In addition, contrast-enhanced CT values correlated with both precontrast T1ρ and T1(Gd) more strongly than with precontrast T2. Finally, T1(Gd) and precontrast T1ρ were found to be moderately correlated with CT data. However, T1(Gd) and precontrast T1ρ were found to be almost completely uncorrelated. Together, these results indicate that T1ρ, T2 and contrast-enhanced techniques may provide complementary information about the molecular environment in cartilage during the evolution of OA.     

The zonal architecture of human articular cartilage described by T2 relaxation time in the presence of Gd-DTPA2-

The depth-wise variation of T(2) relaxation time is known to reflect the collagen network architecture in cartilage, while the delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique is sensitive to tissue proteoglycan (PG) concentration. As the cartilage PG content varies along the tissue depth, the depth-dependent accumulation of the contrast agent may affect the inherent T(2) of cartilage in a nonconstant manner. Therefore, T(2) and dGEMRIC are typically measured in separate MRI sessions. In the present in vitro MRI study at 9.4 T, depth-wise T(2) profiles and collagenous zone thicknesses as determined from T(2) maps in the absence and presence of Gd-DTPA(2-) (T(2) and T(2Gd), respectively) were compared in samples of intact human articular cartilage (n=65). These T(2) measures were further correlated with birefringence (BF) of polarized light microscopy (PLM) to quantify the ability of MRI to predict the properties of the collagen fibril network. The reproducibility of the T(2) measurement in the current setup was also studied. Typical tri-laminar collagen network architecture was observed both with and without Gd-DTPA(2-). The inverse of BF (1/BF) correlated significantly with both T(2) and T(2Gd) (r=0.91, slope=0.56 and r=0.90, slope=0.63), respectively. The statistically significant linear correlations between zone thicknesses as determined from T(2) and T(2Gd) were r=0.55 (slope=0.49), r=0.74 (slope=0.71) and r=0.95 (slope=0.94) for superficial, middle and deep tissue zones, respectively. Reproducibility of the T(2) measurement was worst for superficial cartilage. Consistent with PLM, T(2) and T(2Gd) measurements reveal highly similar depth-dependent information on collagen network in intact human cartilage. Thus, dGEMRIC and T(2) measurements in one MRI session are feasible for intact articular cartilage in vitro.     

Mechanism of disease in early osteoarthritis: application of modern MR imaging techniques — a technical report

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1ρ relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MRI sequence, T1ρ, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-weighted sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future.