Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Cardiothoracic and Vascular Surgery Implant Compatibility With Ultrahigh Field Magnetic Resonance Imaging (4.7 Tesla and 7 Tesla).

The use of 7 Tesla (T) magnetic resonance imaging (MRI) is expanding across medical specialties, particularly, clinical neurosciences and orthopedics. Investigational 7 T MRI has also been performed in cardiology. A limiting factor for expansion of the role of 7 T, irrespective of the body part being imaged, is the sparse testing of biomedical implant compatibility at field strengths >3 T. Implant compatibility can be tested following the American Society for Testing and Materials International guidelines. To assess the current state of cardiovascular implant safety at field strengths >3 T, a systematic search was performed using PubMed, Web of Science, and citation matching. Studies written in English that included at least 1 cardiovascular-related implant and at least 1 safety outcome (deflection angle, torque, or temperature change) were included. Data were extracted for the implant studied, implant composition, deflection angle, torque, and temperature change, and the American Society for Testing and Materials International standards were followed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines for scoping reviews were followed. A total of 9 studies were included. A total of 34 cardiovascular-related implants tested ex vivo at 7 T and 91 implants tested ex vivo at 4.7 T were included. The implants included vascular grafts and conduits, vascular access ports, peripheral and coronary stents, caval filters, and artificial valves. A total of 2 grafts, 1 vascular access port, 2 vena cava filters, and 5 stents were identified as incompatible with the 7 T MRI. All incompatible stents were 40 mm in length. Based on the safety outcomes reported, we identify several implants that may be compatible with >3 T MRI. This scoping review seeks to concisely summarize all the cardiovascular-related implants tested for ultrahigh field MRI compatibility to date.

Chemical exchange rotation transfer imaging of phosphocreatine in muscle.

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.

Increased Number of Circulating CD8/CD26 T Cells in the Blood of Duchenne Muscular Dystrophy Patients Is Associated with Augmented Binding of Adenosine Deaminase and Higher Muscular Strength Scores.

Duchenne muscular dystrophy (DMD) is an X-linked disorder that leads to cardiac and skeletal myopathy. The complex immune activation in boys with DMD is incompletely understood. To better understand the contribution of the immune system into the progression of DMD, we performed a systematic characterization of immune cell subpopulations obtained from peripheral blood of DMD subjects and control donors. We found that the number of CD8 cells expressing CD26 (also known as adenosine deaminase complexing protein 2) was increased in DMD subjects compared to control. No differences, however, were found in the levels of circulating factors associated with pro-inflammatory activation of CD8/CD26 cells, such as tumor necrosis factor-α (TNFα), granzyme B, and interferon-γ (IFNγ). The number of CD8/CD26 cells correlated directly with quantitative muscle testing (QMT) in DMD subjects. Since CD26 mediates binding of adenosine deaminase (ADA) to the T cell surface, we tested ADA-binding capacity of CD8/CD26 cells and the activity of bound ADA. We found that mononuclear cells (MNC) obtained from DMD subjects with an increased number of CD8/CD26 T cells had a greater capacity to bind ADA. In addition, these MNC demonstrated increased hydrolytic deamination of adenosine to inosine. Altogether, our data demonstrated that (1) an increased number of circulating CD8/CD26 T cells is associated with preservation of muscle strength in DMD subjects, and (2) CD8/CD26 T cells from DMD subjects mediated degradation of adenosine by adenosine deaminase. These results support a role for T cells in slowing the decline in skeletal muscle function, and a need for further investigation into contribution of CD8/CD26 T cells in the regulation of chronic inflammation associated with DMD.

Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction.

BACKGROUND: Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation. METHODS: We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine fiber type and size, Pax-7-positive (satellite) cells, and extracellular matrix (via wheat germ agglutinin straining). Using the diffusion tensor imaging data, the fiber tract length, pennation angle, and muscle volume were determined, yielding the physiological cross-sectional area (PCSA). Paired t tests were used to compare the effects of the injury between injured and uninjured limbs and the effects of surgery and rehabilitation within the injured limb. RESULTS: We found significant reductions before surgery in type-IIA muscle cross-sectional area (CSA; p = 0.03), extracellular matrix (p < 0.01), satellite cells per fiber (p < 0.01), pennation angle (p = 0.03), muscle volume (p = 0.02), and PCSA (p = 0.03) in the injured limb compared with the uninjured limb. Following surgery, these alterations in the injured limb persisted and the frequency of the IIA fiber type decreased significantly (p < 0.01) and that of the IIA/X hybrid fiber type increased significantly (p < 0.01). CONCLUSIONS: Significant and prolonged differences in muscle quality and morphology occurred after ACL injury and persisted despite reconstruction and extensive physical therapy. CLINICAL RELEVANCE: These results suggest the need to develop more effective early interventions following an ACL tear to prevent deleterious alterations within the quadriceps.

Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.

MRI techniques: a review and update for the orthopaedic surgeon.

MRI plays a critical role in all orthopaedic practices. A basic working knowledge of the most commonly used pulse sequences in musculoskeletal imaging and the appearance of normal tissues on those sequences is critical to confident MRI interpretation. The orthopaedic surgeon should be familiar with appropriate use of intravenous and intra-articular contrast and its limitations. Concepts key to MRI interpretation include image contrast and resolution, signal, noise, and pulse sequence. Recent advances in anatomic and functional imaging highlight the robust potential of MRI for musculoskeletal evaluation. As MRI technology evolves, the orthopaedic surgeon must stay current on these technologic advances to use this tool to its fullest potential.

Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.

OBJECTIVE: Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver. RESEARCH DESIGN AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon receptor null (gcgr(-/-)) and wild-type (gcgr(+/+)) littermate mice were subsequently fed HFD to provoke moderate fatty liver and then performed either 10 or 6 weeks of running wheel or treadmill exercise, respectively. RESULTS: Exercise reverses progression of HFD-induced fatty liver in gcgr(+/+) mice. Remarkably, such changes are absent in gcgr(-/-) mice, thus confirming the hypothesis that exercise-stimulated hepatic glucagon receptor activation is critical to reduce HFD-induced fatty liver. CONCLUSIONS: These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

Buckle fractures in children: Is urgent treatment necessary?

PURPOSE: To determine whether the clinical outcome of buckle fractures in children differs between those treated acutely on the same day of trauma and those treated subacutely, and whether a change in practice patterns based on these data would result in cost savings. METHODS: In this retrospective cohort study-approved by the institutional review board-we reviewed the cases of 341 consecutive patients younger than 18 years of age seen by the pediatric orthopedic clinic for treatment of isolated extremity buckle fractures between July 1, 2004 and August 31, 2007. Time from injury to treatment was used to divide patients into 2 groups: acute (1 day or less; n=155) and subacute treatment (more than 1 day; n=186). Clinical outcome at final orthopedic follow-up was recorded for each patient. We defined adverse outcome as fractures requiring manipulation, clinically apparent deformity, or functional impairment. Charge analysis compared differences in management costs for patients with buckle fractures presenting initially to the emergency department (ED) and those seen solely in the orthopedic clinic. RESULTS: No adverse outcomes were identified in either acute or subacute treatment groups. Total clinical visits did not vary (acute, 3.2 vs subacute, 3.1; P=.051). Presence of mild angulation of fractures on radiographs did not differ significantly between acute and subacute management groups at initial presentation (6.5% vs 8.6%; P=.541) or at final follow-up (12.2% vs 12.4%; P=1.0). A cost savings of approximately $3000 could have been realized for each patient referred to the ED who might otherwise have been seen subacutely in the orthopedic clinic. CONCLUSIONS: No adverse clinical outcomes resulted from subacute treatment of stable buckle fractures. Cost and time savings may be realized with subacute management of buckle fractures without affecting clinical outcome.