Faculty Bibliography

OBJECTIVE: To evaluate healthy skeletal muscle pre- and post-exercise via 7 T (23)Na MRI and muscle proton T(2) mapping, and to evaluate diabetic muscle pre- and post-exercise via 7 T (23)Na MRI. METHODS: The calves of seven healthy subjects underwent imaging pre- and post-exercise via 7 T (23)Na MRI (3D fast low angle shot, TR/TE = 80 ms/0.160 ms, 4 mm x 4 mm x 4 mm) and 1 week later by (1)H MRI (multiple spin-echo sequence, TR/TE = 3,000 ms/15-90 ms). Four type 2 diabetics also participated in the (23)Na MRI protocol. Pre- and post-exercise sodium signal intensity (SI) and proton T(2) relaxation values were measured/calculated for soleus (S), gastrocnemius (G), and a control, tibialis anterior (TA). Two-tailed t tests were performed. RESULTS: In S/G in healthy subjects post-exercise, sodium SI increased 8-13% (p < 0.03), then decreased (t (1/2) = 22 min), and (1)H T(2) values increased 12-17% (p < 0.03), then decreased (t (1/2 )= 12-15 min). In TA, no significant changes in sodium SI or (1)H T(2) values were seen (-2.4 to 1%, p > 0.17). In S/G in diabetics, sodium SI increased 10-11% (p < 0.04), then decreased (t (1/2) = 27-37 min) without significant change in the TA SI (-3.6%, p = 0.066). CONCLUSION: It is feasible to evaluate skeletal muscle via 3D (23)Na MRI at 7 T. Post-exercise muscle (1)H T(2) values return to baseline more rapidly than sodium SI. Diabetics may demonstrate delayed muscle sodium SI recovery compared with healthy subjects

OBJECTIVE: To assess the relationship between T2 values of femorotibial cartilage and knee alignment in patients with clinical symptoms of medial osteoarthritis (OA). METHODS: Twenty-four patients (mean age +/- standard deviation, 62.5 +/- 9.9 years) with clinical symptoms of medial knee OA, 12 with varus and 12 with valgus alignment of the femorotibial joint, were investigated on 3T MR using a 2D multi-echo spin echo (MESE) sequence for T2 mapping. Analysis of covariance, Spearman correlation coefficients, exact Mann-Whitney tests, and Fisher's exact tests were used for statistical analysis. RESULTS: Overall the T2 values of cartilage in the medial compartment (median +/- interquartile-range, 49.44 +/- 6.58) were significantly higher (P = 0.0043) than those in the lateral compartment (47.15 +/- 6.87). Patients with varus alignment (50.83 +/- 6.30 ms) had significantly higher T2 values of cartilage (P < 0.0001) than patients with valgus alignment (46.20 +/- 6.00 ms). No statistically significant association between the T2 values of cartilage (in either location) and the Kellgren Lawrence score was found in the varus or in the valgus group. CONCLUSION: T2 measurements were increased in medial knee OA patients with varus alignment, adding support to the theory of an association of OA and joint alignment

Ultra-high field (UHF; >or=7 T) magnetic resonance imaging (MRI), with its greater signal-to-noise ratio, offers the potential for increased spatial resolution, faster scanning, and, above all, improved biochemical and physiological imaging of skeletal muscle. The increased spectral resolution and greater sensitivity to low-gamma nuclei available at UHF should allow techniques such as (1)H MR spectroscopy (MRS), (31)P MRS, and (23)Na MRI to be more easily implemented. Numerous technical challenges exist in the performance of UHF MRI, including changes in relaxation values, increased chemical shift and susceptibility artifact, radiofrequency (RF) coil design/B (1)(+) field inhomogeneity, and greater RF energy deposition. Nevertheless, the possibility of improved functional and metabolic imaging at UHF will likely drive research efforts in the near future to overcome these challenges and allow studies of human skeletal muscle physiology and pathophysiology to be possible at >or=7 T

PURPOSE:: To determine the feasibility of performing MRI of the wrist at 7 Tesla (T) with parallel imaging and to evaluate how acceleration factors (AF) affect signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and image quality. MATERIALS AND METHODS:: This study had institutional review board approval. A four-transmit eight-receive channel array coil was constructed in-house. Nine healthy subjects were scanned on a 7T whole-body MR scanner. Coronal and axial images of cartilage and trabecular bone micro-architecture (3D-Fast Low Angle Shot (FLASH) with and without fat suppression, repetition time/echo time = 20 ms/4.5 ms, flip angle = 10 degrees , 0.169-0.195 x 0.169-0.195 mm, 0.5-1 mm slice thickness) were obtained with AF 1, 2, 3, 4. T1-weighted fast spin-echo (FSE), proton density-weighted FSE, and multiple-echo data image combination (MEDIC) sequences were also performed. SNR and CNR were measured. Three musculoskeletal radiologists rated image quality. Linear correlation analysis and paired t-tests were performed. RESULTS:: At higher AF, SNR and CNR decreased linearly for cartilage, muscle, and trabecular bone (r < -0.98). At AF 4, reductions in SNR/CNR were:52%/60% (cartilage), 72%/63% (muscle), 45%/50% (trabecular bone). Radiologists scored images with AF 1 and 2 as near-excellent, AF 3 as good-to-excellent (P = 0.075), and AF 4 as average-to-good (P = 0.11). CONCLUSION:: It is feasible to perform high resolution 7T MRI of the wrist with parallel imaging. SNR and CNR decrease with higher AF, but image quality remains above-average. J. Magn. Reson. Imaging 2010;31:740-746. (c) 2010 Wiley-Liss, Inc

PURPOSE: 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. MATERIALS AND METHODS: Five healthy controls (four males, one female; mean +/- standard deviation [SD] age 28.7 +/- 4.8 years) and five patients with osteoarthritis (OA) (three males, two females; mean +/- SD age 52.4 +/- 5.6 years) underwent (23)Na MRI on a 7T, multinuclei equipped whole-body scanner. A quadrature (23)Na knee coil and a 3D-gradient echo (GRE) imaging sequence with a radial acquisition were utilized. Cartilage sodium concentration was measured and compared between the healthy controls and OA patients. RESULTS: The average signal-to-noise ratio (SNR) for different spatial resolutions (1.2-4 mm) varied from approximately 14-120, respectively. The mean sodium concentration of healthy subjects ranged from approximately 240 +/- 28 mM/L to 280 +/- 22 mM/L. However, in OA patients the sodium concentrations were reduced significantly by approximately 30%-60%, depending on the degree of cartilage degeneration. CONCLUSION: The preliminary results suggest that sodium imaging at 7T may be a feasible potential alternative for physiologic OA imaging and clinical diagnosis. J. Magn. Reson. Imaging 2009;30:606-614. (c) 2009 Wiley-Liss, Inc

We investigated how cortical bone, trabecular bone, and muscle adapt in US Olympic Fencing Team members. These athletes demonstrate femoral cortical bone expansion, greater distal femoral trabecular bone density, and greater muscle mass compared to controls. This is the first study to investigate musculoskeletal adaptations in Olympic fencers. PURPOSE: Wolff's law states that bone remodels according to mechanical forces placed upon it. Our goal was to determine how cortical and trabecular bone adapt in Olympic athletes who perform intermittent high-impact activity. MATERIALS AND METHODS: Nine males from the 2004 US Olympic Fencing Team and nine matched controls were evaluated by quantitative computed tomography. Femurs were scanned at 50% and 75% along the shaft. We evaluated cortical thickness (C.Th), cortical (C.Ar), trabecular (Tb.Ar), and total bone areas (Tot.Ar), proportions of C.Ar and Tb.Ar to Tot.Ar, cortical (C.BMD.), trabecular (Tb.MBD), and total bone densities (Tot.BMD), muscle (M.Ar), and thigh areas (Th.Ar). RESULTS: Fencers had greater C.Th (+24.5 to 38.8%), C.Ar (+16.9 to 19.6%), C.Ar/Tot.Ar (+6.3 to 16.3%), and lower Tb.Ar/Tot.Ar (-23.5% to -23.8%; p<0.05). Fencers demonstrated a positive difference in C.Th in the dominant vs. nondominant thigh at 50% (+5.4%, p = 0.040) and at 75% (+13.8%, p = 0.048 by analysis of covariance). Fencers had 54% greater Tb.BMD at 75% (p = 0.025), but not at 50% (p = 0.63). There was no difference between groups for C.BMD (p = .66 at 50%, p = 0.88 at 75%). Fencers had greater M.Ar (+30%) and asymmetrically greater M.Ar (+12.2%) in the dominant thigh (p < 0.004). CONCLUSION: In world-class athletes who perform intermittent, high-impact activity, cortical bone expands, trabecular bone density is greater, and muscle mass is greater. This is the first study to examine musculoskeletal adaptations in Olympic fencers

Magnetic resonance imaging (MRI) at 7.0 T has the potential for higher signal-to-noise ratio (SNR), improved spectral resolution, and faster imaging compared with 1.5-T and 3.0-T MR systems. This is especially interesting for challenging imaging regions like the wrist and the hand because of the small size of the visualized anatomical structures; the increase in SNR could then be directly converted into higher spatial resolution of the images. Practically, imaging at 7.0 T poses a variety of technical challenges such as static (B (0)) and radiofrequency (B (1)) homogeneities, shimming, chemical shift artifacts, susceptibility artifacts, alterations in tissue contrast, specific absorption rate limitations, coil construction, and pulse sequence tuning. Despite these limitations, this first experience in anatomical imaging of the wrist and the hand at 7.0 T is very promising. Functional imaging techniques will gain importance at ultra-high-field MRI and need to be assessed in detail in the future

PURPOSE: To produce in vivo high-resolution images of the knee and to determine the feasibility of using 7T MR to detect changes in trabecular bone microarchitecture in elite athletes (Olympic fencers) who undergo high impact activity. MATERIALS AND METHODS: The dominant knees of four males from the U.S. Olympic Fencing Team and three matched healthy male controls were scanned in a 7T whole-body scanner using a quadrature knee coil with three-dimensional (3D) fast low angle shot (FLASH): 50 axial images at the distal femur (0.156 mm x 0.156 mm) and 80 axial images at the knee joint (0.195 mm x 0.195 mm). Bone volume fraction (BVF) and marrow volume fraction (MVF) images were computed and fuzzy distance transform (FDT) and digital topological analysis (DTA) were applied to determine: trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp); BVF (BV/TV); trabecular and marrow space surface-to-curve ratio (SC, marker of plate to rod ratio); and trabecular and marrow space erosion index (EI, inverse marker for network connectivity). Quadriceps muscle volume (MV) was calculated as well. We calculated group means and performed two-tailed t-tests to determine statistical significance. RESULTS: Compared to controls, fencers had: decreased Tb.Sp (P = 0.0082 at femur, P = 0.051 at joint); increased Tb.N (P < 0.05 at both femur and joint) and BV/TV (P < 0.001 at both femur and joint); increased trabecular SC and decreased marrow space SC (P < 0.01 at both femur and joint); decreased trabecular EI and increased marrow space EI (P < 0.01 at both femur and joint); and increased MV (P = 0.038). There was no difference in Tb.Th at the distal femur (P = 0.92) or joint (P = 0.71) between groups. CONCLUSION: To our knowledge, this is the first study to perform 7T MRI of the knee in vivo. Elite athletes who undergo high impact activity have increased MV and improved trabecular bone structure compared to controls

Cofilin, in its Ser3 dephosphorylated form, accelerates actin filament turnover in cells. We report here the role of cofilin in platelet actin assembly. Cofilin is primarily phosphorylated in the resting platelet as evidenced by a specific antibody directed against its Ser3 phosphorylated form. After stimulation with thrombin under nonstirring conditions, cofilin is reversibly dephosphorylated and transiently incorporates into the actin cytoskeleton. Its dephosphorylation is maximal 1-2 min after platelet stimulation, shortly after the peak of actin assembly occurs. Cofilin rephosphorylation begins 2 min after activation and exceeds resting levels by 5-10 min. Cofilin is dephosphorylated with identical kinetics but fails to become rephosphorylated when platelets are stimulated under stirring conditions. Cofilin is normally rephosphorylated when platelets are stimulated in the presence of Arg-Gly-Asp-Ser (RGDS) peptide or wortmannin to block alpha(IIb)beta3 cross-linking and signaling or in platelets isolated from a patient with Glanzmann thrombasthenia, which express only 2-3% of normal alpha(IIb)beta3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation in the platelet actin cytoskeleton are decreased when alpha(IIb)beta3 is engaged. Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets

Molecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody-mediated immune responses to shared viral-host antigens have been associated with the development of disease in these patients. Patients infected with human T-lymphotropic virus type I (HTLV-I) develop HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody-mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV-I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33-kd band in all HAM/TSP patients tested. By contrast, no neuron-specific IgG reactivity could be demonstrated from HTLV-I seronegative controls and, more important, from HTLV-I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV-I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV-I tax (an immunodominant HTLV-I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV-I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV-I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV-I, suggesting viral-specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP