Faculty Bibliography

The rate of phosphocreatine (PCr) resynthesis after physical exercise has been extensively studied with phosphorus ((31) P)-MRS. Previous studies have used small surface coils that were limited to measuring one superficial muscle per experiment. This study focuses on the development and implementation of a spectrally selective three-dimensional turbo spin echo (3D-TSE) sequence at 3T and 7T with temporal resolution of 24 s, using two geometrically identical volume coils. We acquired imaging data of PCr recovery from four healthy volunteers and one diabetic patient, who performed plantar flexions using resistance bands. We segmented the anatomical regions of six different muscles from the lower leg, namely the gastrocnemius [lateral (GL) and medial (GM)], the tibialis [anterior (TA) and posterior (TP)], the soleus (S) and the peroneus (P) and measured the local PCr resynthesis rate constants. During the same examination, we also acquired unlocalized (31) P-MRS data at a temporal resolution of 6 s. At 3T, the PCr resynthesis rate constants were measured at 25.4 +/- 3.7 s [n = 4, mean +/- standard deviation (SD)] using the MRS method and 25.6 +/- 4.4 s using the MRI method. At 7T, the measured rates were 26.4 +/- 3.2 s and 26.2 +/- 4.7 s for MRS and MRI. Using our imaging method, we measured the local PCr resynthesis rate constants in six individual muscles of the lower leg (min/max 20.2/31.7 s). The recovery rate constants measured for the diabetic patient were 55.5 s (MRS) and 52.7 s (MRI). The successful implementation of our 3D-method suggests that imaging is possible at both fields with a relatively high spatial resolution (voxel size: 4.2 mL at 3T and 1.6 mL at 7T) using volume coils and that local PCr resynthesis rates can be obtained in a single measurement. The advantage of the imaging method is that it can highlight differences in PCr resynthesis rates between different muscles in a single measurement in order to study spatial gradients of metabolic properties of diseased states for which very little is currently known

The clinical diagnosis of osteoporosis has evolved over the past 20 years to emphasize the relationship between compromised bone strength and fracture susceptibility. The goal of treatment of osteoporosis is fracture prevention. The aging of the American population will place additional burdens on our healthcare system among which will be the need to treat and prevent the estimated increase in fracture rates projected over the next 10 years. There is a significant number of currently available bone strengthening medications used in the treatment of osteoporosis, and this report highlights the effects of these drugs on bone mineral density values and on the relative rates of fragility fractures when these drugs are compared to placebo in clinical trials of subjects with osteoporosis. Identifying those individuals most in need of immediate treatment to prevent fractures remains a challenge despite the use of fracture risk assessment tools, which assess bone mineral density and clinical parameters in order to define an individual's risk of fracture over a finite period of time. Newer tools that may help better define bone strength (resistance to fracture) include high resolution MRI and finite element analysis of the MRI generated images, and this technology and our experience with it is briefly reviewed in this report. There are a number of new classes of drugs in development for the treatment of osteoporosis, and the clinician is likely to have additional antiresorptive and anabolic agents as treatment options for this condition over the next few years.

OBJECTIVE: To assess and compare subregional and whole T1rho values (median+/-interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren-Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. MATERIALS AND METHODS: 30 subjects with varying degrees of OA (KL1-4, 13 females, 17 males, mean age+/-SD=63.9+/-13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. RESULTS: Lateral (72+/-10ms, median+/-interquartile range) and medial (65+/-10ms) femoral anterior cartilage subregions in moderate-severe OA subjects had significantly higher T1rho values (P<0.05) than cartilage subregions and whole femorotibial cartilage in doubtful-minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate-severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful-minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5-6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0-1 (normal). CONCLUSION: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with osteoarthritis

Osteoarthritis is a degenerative disease of articular cartilage that may be associated with a loss of glycosaminoglycans. Quantitative sodium magnetic resonance imaging is highly specific to glycosaminoglycan content and could be used to assess the biochemical degradation of cartilage in early osteoarthritis. However, the reproducibility and repeatability of this technique are not well documented. The aim of this study is to test the reproducibility and repeatability of sodium quantification in cartilage in vivo using intraday and interday acquisitions at 3 T and 7 T, with a radial 3D sequence, with and without fluid suppression. Fluid suppression was obtained by adiabatic inversion recovery (IR WURST) and is expected to improve the sensitivity of the method to glycosaminoglycan content. The root mean square of coefficients of variation are all in the range of 7.5-13.6%. No significant intermagnet, intersequence, intraday, and interday differences in the coefficients of variation were observed. Sodium quantification using IR WURST gave values closer to those reported in the literature for healthy cartilage (220-310 mM) than radial 3D. In conclusion, IR WURST was more accurate in context of sodium measurement, with a reproducibility and repeatability comparable to other compositional magnetic resonance imaging techniques of cartilage. Magn Reson Med, 2011. (c) 2011 Wiley Periodicals, Inc.

OBJECTIVES: To evaluate cartilage repair and native tissue using a three-dimensional (3D), radial, ultra-short echo time (UTE) (23)Na MR sequence without and with an inversion recovery (IR) preparation pulse for fluid suppression at 7 Tesla (T). METHODS: This study had institutional review board approval. We recruited 11 consecutive patients (41.5 +/- 11.8 years) from an orthopaedic surgery practice who had undergone a knee cartilage restoration procedure. The subjects were examined postoperatively (median = 26 weeks) with 7-T MRI using: proton-T2 (TR/TE = 3,000 ms/60 ms); sodium UTE (TR/TE = 100 ms/0.4 ms); fluid-suppressed, sodium UTE adiabatic IR. Cartilage sodium concentrations in repair tissue ([Na(+)](R)), adjacent native cartilage ([Na(+)](N)), and native cartilage within the opposite, non-surgical compartment ([Na(+)](N2)) were calculated using external NaCl phantoms. RESULTS: For conventional sodium imaging, mean [Na(+)](R), [Na(+)](N), [Na(+)](N2) were 177.8 +/- 54.1 mM, 170.1 +/- 40.7 mM, 172.2 +/- 30 mM respectively. Differences in [Na(+)](R) versus [Na(+)](N) (P = 0.59) and [Na(+)](N) versus [Na(+)](N2) (P = 0.89) were not significant. For sodium IR imaging, mean [Na(+)](R), [Na(+)](N), [Na(+)](N2) were 108.9 +/- 29.8 mM, 204.6 +/- 34.7 mM, 249.9 +/- 44.6 mM respectively. Decreases in [Na(+)](R) versus [Na(+)](N) (P = 0.0.0000035) and [Na(+)](N) versus [Na(+)](N2) (P = 0.015) were significant. CONCLUSIONS: Sodium IR imaging at 7 T can suppress the signal from free sodium within synovial fluid. This may allow improved assessment of [Na(+)] within cartilage repair and native tissue. KEY POINTS : * NaIR magnetic resonance imaging can suppress signal from sodium within synovial fluid. * NaIR MRI thus allows assessment of sodium concentration within cartilage tissue alone. * This may facilitate more accurate assessment of repair tissue composition and quality.

The compartment-specific lipid changes in femoral-tibial bone of healthy controls and mild osteoarthritis (OA) patients were quantified at 3.0 T. Healthy volunteers [Kellgren-Lawrence (KL) grade = 0; n = 15, 4 females, 11 males, mean age 39 +/- 16 years, age range = 24-78 years] and mild OA patients (KL = 1, 2; n = 26, 12 females, 14 males, mean age 61 +/- 14 years, age range = 27-80 years) were scanned on a 3 T scanner. Clinical proton density (PD)-weighted fast spin echo (FSE) images in the sagittal (without fat-saturation), axial and coronal (fat-saturation) planes were acquired for cartilage Whole-Organ MR Imaging Score (WORMS) grading. A voxel of 10 x 10 x 10 mm(3) was positioned in the medial and lateral compartments of the tibia [medial tibial (MT) and lateral tibial (LT)] and femur [medial femoral (MF) and lateral femoral (LF)] for MRS measurements using the single voxel-stimulated echo acquisition mode (STEAM) pulse sequence. All MRS data were processed with Java-based Magnetic Resonance User Interface (JMRUI). Wilcoxon's rank sum test and mixed model two-way analysis of variance (anova) were performed to determine significant differences between different compartments as well as examine the effect of OA grade and compartment, and their interactions. Generally, the MF compartment index of unsaturation was increased in healthy subjects compared with OA subjects (whether graded by KL or WORMS score). Differences between MF at KL0 and all other compartments at KL1 except LF approached statistical significance (p < 0.05). Differences in saturated lipids signals could be observed predominantly in the 2.03 p.p.m. frequency shift. Healthy controls in the MF compartment had the lowest saturated lipid signals, and mild OA patients with KL2 and WORMS5-6 in the MF compartment had the highest saturated lipid signals compared with other compartments at 2.03 p.p.m. (p < 0.05).

The goal of this study was to demonstrate the feasibility of using 7-Tesla (7T) magnetic resonance imaging (MRI) and micro-finite element analysis (microFEA) to evaluate mechanical and structural properties of whole, cortical, and trabecular bone at the distal femur and proximal tibia in vivo. 14 healthy subjects were recruited (age 40.7 +/- 15.7 years). The right knee was scanned on a 7T MRI scanner using a 28 channel-receive knee coil and a three-dimensional fast low-angle shot sequence (TR/TE 20 ms/5.02 ms, 0.234 mm x 0.234 mm x 1 mm, 80 axial images, 7 min 9 s). Bone was analyzed at the distal femoral metaphysis, femoral condyles, and tibial plateau. Whole, cortical, and trabecular bone stiffness was computed using microFEA. Bone volume fraction (BVF), bone areas, and cortical thickness were measured. Trabecular bone stiffness (933.7 +/- 433.3 MPa) was greater than cortical bone stiffness (216 +/- 152 MPa) at all three locations (P < 0.05). Across locations, there were no differences in bone stiffness (whole, cortical, or trabecular). Whole, cortical, and trabecular bone stiffness correlated with BVF (R >/= 0.69, P < 0.05) and inversely correlated with corresponding whole, cortical, and trabecular areas (R 0.05). Whole, cortical, and trabecular stiffness correlated with body mass index (R >/= 0.62, P < 0.05). In conclusion, at the distal femur and proximal tibia, trabecular bone contributes 66-74% of whole bone stiffness. 7T MRI and microFEA may be used as a method to provide insight into how structural properties of cortical or trabecular bone affect bone mechanical competence in vivo.

PURPOSE: To compare a new birdcage-transmit, 28-channel receive array (28-Ch) coil and a quadrature volume coil for 7T morphologic MRI and T2 mapping of knee cartilage. MATERIALS AND METHODS: The right knees of 10 healthy subjects were imaged on a 7T whole body magnetic resonance (MR) scanner using both coils. 3D fast low-angle shot (3D-FLASH) and multiecho spin-echo (MESE) sequences were implemented. Cartilage signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), thickness, and T2 values were assessed. RESULTS: SNR/CNR was 17%-400% greater for the 28-Ch compared to the quadrature coil (P </= 0.005). Bland-Altman plots show mean differences between measurements of tibial/femoral cartilage thickness and T2 values obtained with each coil to be small (-0.002 +/- 0.009 cm / 0.003 +/- 0.011 cm) and large (-6.8 +/- 6.7 msec/-8.2 +/- 9.7 msec), respectively. For the 28-Ch coil, when parallel imaging with acceleration factors (AF) 2, 3, and 4 was performed SNR retained was: 62%-69%, 51%-55%, and 39%-45%. CONCLUSION: A 28-Ch knee coil provides increased SNR/CNR for 7T cartilage morphologic imaging and T2 mapping. Coils should be switched with caution during clinical studies because T2 values may differ. The greater SNR of the 28-Ch coil could be used to perform parallel imaging with AF2 and obtain similar SNR as the quadrature coil. J. Magn. Reson. Imaging 2012;441-448. (c) 2011 Wiley Periodicals, Inc

Sodium MRI has been shown to be highly specific for glycosaminoglycan (GAG) content in articular cartilage, the loss of which is an early sign of osteoarthritis (OA). Quantitative sodium MRI techniques are therefore under development in order to detect and assess early biochemical degradation of cartilage, but due to low sodium NMR sensitivity and its low concentration, sodium images need long acquisition times (15-25min) even at high magnetic fields and are typically of low resolution. In this preliminary study, we show that compressed sensing can be applied to reduce the acquisition time by a factor of 2 at 7T without losing sodium quantification accuracy. Alternatively, the nonlinear reconstruction technique can be used to denoise fully-sampled images. We expect to even further reduce this acquisition time by using parallel imaging techniques combined with SNR-improved 3D sequences at 3T and 7T

The past year has been a dynamic one for clinicians and researchers with an interest in osteoporosis. This update will focus on the issue of the relationship between bisphosphonate treatment and atypical femoral fractures, highlight the advances in imaging techniques that are increasingly being studied as adjuncts to bone density testing, and explore re- cent evidence that suggests that osteoporosis medications may be linked to an increase in life expectancy. Since the first case reports describing unusual femur fractures in long term users of bisphosphonates began to appear, there has been great interest in identifying why and whether this class of drug can cause these atypical fractures. There have been a significant number of large studies that seem to suggest that these fractures do occur with an increased frequency among subjects who have used bisphosphonates over an extended period of time, but that these events are relatively rare. The occurrence of these fractures have helped to fashion new treatment regimens with periods of "drug holidays" often recommended to people with lower short-term and intermediate-term fracture risk. It is important to remind the reader that bisphosphonates prevent many typical hip and vertebral compression fractures, particularly in the higher risk elderly patient and that a rational balance be struck so that those in need of continued osteoporosis treatment receive it. Advances in imaging, such as high resolution MRI and peripheral micro CT scanners, are allowing investigators to non-invasively assess bone microarchitecture and bone stiffness of individuals as a means of trying to more accurately define those subjects who might be at increased risk of fracture and who might benefit from bone strengthening medication. Finally, this update will briefly review the emerging data that suggests that anti-resorptive medication may extend life expectancy beyond that which can be expected solely by reducing the incidence of future fractures.