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OBJECTIVES: Our previous published studies have focused on safety and effectiveness of using therapeutic ultrasound (TUS) for treatment of type 2 diabetes mellitus (T2DM) in preclinical models. Here we present a set of simulation studies to explore potential ultrasound application schemes that would be feasible in a clinical setting. METHODS: Using the multiphysics modeling tool OnScale, we created two-dimensional (2D) models of the human abdomen from CT images captured from one normal weight adolescent patient, and one obese adolescent patient. Based on our previous studies, the frequency of our TUS was 1 MHz delivered from a planar unfocused transducer. We tested five different insonation angles, as well as four ultrasound intensities combined with four different duty factors and five durations of application to explore how these variables effect the peak pressure and temperature delivered to the pancreas as well as surrounding tissue in the model. RESULTS: We determined that ultrasound applied directly from the anterior of the patient abdomen at 5 W/cm2 delivered consistent acoustic pressures to the pancreas at the levels which we have previously found to be effective at inducing an insulin release from preclinical models. CONCLUSIONS: Our modeling work indicates that it may be feasible to non-invasively apply TUS in clinical treatment of T2DM.
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Cavidad Abdominal , Diabetes Mellitus Tipo 2 , Obesidad Infantil , Humanos , Adolescente , Insulina/uso terapéutico , Páncreas/diagnóstico por imagenRESUMEN
To the best of our knowledge, therapeutic ultrasound (TUS) is thus far an unexplored means of delivering mechanical stimulation to cardiomyocyte cultures, which is necessary to engineer a more mature cardiomyocyte phenotype in vitro. Spectral ultrasound (SUS) may provide a way to non-invasively, non-disruptively and inexpensively monitor growth and change in cell cultures over long periods. Compared with other measurement methods, SUS as an acoustic measurement tool will not be affected by an acoustic therapy, unlike electrical measurement methods, in which motion caused by acoustic therapy can affect measurements. Further SUS has the potential to provide functional as well as morphological information in cell cultures. Human induced pluripotent stem cell cardiomyocytes (iPS-CMs) were imaged with calcium fluorescence microscopy while TUS was being applied. TUS was applied at 600 kHz and 1, 3.4 and 6 W/cm2 for a continuous 1 s pulse. Measures of the instantaneous beat frequency, repolarization rate and calcium spike amplitude were calculated from the fluorescence data. At 600 kHz, TUS at 1 and 6 W/cm2 had significant effects on the shortening of both the repolarization rate and instantaneous beat rate of the iPS-CMs (p < 0.05), while TUS at 3.4 and 6 W/cm2 had significant effects on the shortening of the calcium spike amplitude (p < 0.05). Three SUS measures and one gray-level measure were captured from the iPS-CM monolayers while they were simultaneously being imaged with calcium-labeled confocal microscopy. The gray-level measure performed the best of all SUS measures; however, it was not reliable enough to produce a consistent determination of the beat rate of the cell. Finally, SUS measures were captured using three different transducers while simultaneously applying TUS. A center-of-mass (COM) measure calculated from the wavelet transform scalogram of the time-averaged radiofrequency data revealed that SUS was able to detect a change in the frequency content of the reflected ultrasound at 1 and 6 W/cm2 before and after ultrasound application (p < 0.05), showing promise for the ability of SUS to measure changes in the beating behavior of iPS-CMs. Overall, SUS is promising as a method for constant monitoring of dynamic cell and tissue culture and growth.
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Células Madre Pluripotentes Inducidas , Terapia por Ultrasonido , Calcio , Humanos , Miocitos Cardíacos , UltrasonografíaRESUMEN
We report a case of a 66-year-old woman who presented with acute shoulder pain. Initial radiographs revealed a sclerotic intraosseous lesion in the greater tuberosity with associated cortical erosions and subacromial calcification. The diagnosis of intraosseous calcific tendinitis was confirmed with additional magnetic resonance imaging and nuclear medicine imaging. Within 3 months of conservative measures, the patient's symptoms improved but the radiographic appearance had become more aggressive with a wider zone of transition. After 1 year, the imaging findings continued to change, with the development of subcortical cysts. Correct diagnosis of this uncommon manifestation of tendinitis requires knowledge of how its appearance changes with time.
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UNLABELLED: Left bundle branch block (LBBB) is common in patients with heart failure (HF) and contributes to left ventricular (LV) dysfunction. The abnormal septal motion may alter septal metabolic demand but this has not been well characterized in patients with ischemic cardiomyopathy (ICM) and LV dysfunction. The aim of this study was to determine the effect of LBBB on septal metabolism in patients with ICM, LV dysfunction, and LBBB. METHODS: Fifty-three patients with LV dysfunction and ICM were identified: 34 with LBBB, 19 with normal QRS (=100, control patients). PET using (18)F-FDG and (82)Rb was used to measure myocardial glucose metabolism and perfusion, respectively. Perfusion-metabolism differences were determined. Scar scores (matched decreases in (18)F-FDG and (82)Rb), mismatch scores (hibernating myocardium with decreased (82)Rb relative to (18)F-FDG), and reverse-mismatch (R-MM) scores (reduced (18)F-FDG relative to (82)Rb) were assessed in the septum and lateral wall. RESULTS: (18)F-FDG uptake in the septum was reduced in patients with LBBB (64.0% +/- 15.4%) compared with control patients (74.9% +/- 14.3%; P < 0.05). Mean septal R-MM was greater in patients with LBBB (19.1% +/- 15.3%) versus control patients (4.7% +/- 10.6%; P < 0.05). However, 32% (11/34) of patients with LBBB did not demonstrate septal R-MM, 91% (10/11) of whom demonstrated lateral wall perfusion defects. Of the 68% (23/34) of patients with LBBB and septal R-MM, 52% (12/23) demonstrated lateral wall perfusion defects (P < 0.05). There was a significant difference in the percentage of the lateral wall with scar between those with septal R-MM (9.3% +/- 10.5%) and those without (19.9% +/- 14.3%; P < 0.05). CONCLUSION: Previously, LBBB was believed to be characterized by reduced glucose metabolism relative to perfusion in the septum; however, this is not always the case in ICM. LBBB is not associated with septal R-MM in >30% of this patient population. Absence of this finding was often associated with lateral wall perfusion defects, suggesting an alteration in the metabolic demand on the septum. This may have implications for HF therapies such as resynchronization and requires further study.
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Cardiomiopatías/patología , Glucosa/metabolismo , Tabiques Cardíacos/metabolismo , Tomografía de Emisión de Positrones/métodos , Anciano , Bloqueo de Rama , Electrocardiografía/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/patología , Miocardio/patología , PerfusiónRESUMEN
UNLABELLED: Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) detects recurrence of papillary thyroid carcinoma (PTC) in thyroidectomized patients with elevated thyroglobulin (Tg) levels and negative (131)I-whole-body scans. This paper describes the utility of thyroid-stimulating hormone (TSH)-stimulated fused FDG-PET/computed tomography (CT) scanning on our first 15 patients of this population. METHODS: Patients were prepared for PET/CT imaging with thyroid hormone withdrawal (n = 7) or recombinant human TSH (n = 8). All other imaging before the PET/CT did not demonstrate evidence of recurrence. RESULTS: PET/CT scans revealed active foci in 9 patients, 4 prepared with hypothyroidism, and 5 with exogenous TSH. Positive results were demonstrated even in those with relatively low stimulated-TSH Tg values (13 and 14 microg/L). Six patients with positive PET/CT scans were treated surgically, yielding malignant tissue for 5 of those patients. CONCLUSION: PET/CT scans performed under TSH stimulation are an effective method of detecting of recurrence of PTC and direct surgical interventions, even in those with persistently elevated but relatively low Tg levels.
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Carcinoma Papilar/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Neoplasias de la Tiroides/diagnóstico por imagen , Tirotropina , Tomografía Computarizada de Emisión , Adulto , Carcinoma Papilar/patología , Reacciones Falso Negativas , Femenino , Fluorodesoxiglucosa F18 , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Tiroglobulina/sangre , Neoplasias de la Tiroides/patologíaRESUMEN
BACKGROUND: Our objectives were to investigate the accuracy of global and regional left ventricular (LV) function parameters determined from gated fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) and to determine whether this approach complements viability imaging data for tissue characterization. Nongated FDG-PET is a clinical standard for viability imaging, but LV function is often determined with other techniques, which increases patient burden, expenditure, and co-registration errors. Better tissue characterization may be achieved if data were acquired with one test. Methods and results Forty-eight patients with LV dysfunction (including 35 with ejection fraction [EF] =35%) underwent perfusion/FDG imaging with gating of the FDG images and radionuclide angiography (RNA) 6 +/- 6 days apart. Regional function (wall motion/thickening) and viability pattern (normal, mismatch, nontransmural scar, and transmural scar) were determined for 301 segments. Global EFs from FDG-PET (29.3% +/- 11.5%) and RNA (31.1% +/- 10.4%) were well correlated: EF(FDG-PET) = 0.91 x EF(RNA) + 0.91 (r = 0.83, P <.00001). Regional wall motion concordance between PET and RNA with three wall motion scores was 67% with moderate agreement (kappa = 0.50, P <.001). PET viability was also determined for each segment. The relative frequency of normal motion compared with abnormal motion decreased with worsening viability classification. Of the normal segments, 96 of 139 (69%) had reduced wall motion, suggesting repetitively stunned myocardium. Segments classified as normal or mismatch had a higher frequency of normal wall thickening (65% and 52%) than wall motion (31% and 17%). No segments classified as transmural scar exhibited normal wall thickening. CONCLUSION: Gated FDG-PET accurately measures global LV function. Regional function can also be determined with reasonable accuracy. This approach also provides precise co-registration of function with metabolic information and thus improved tissue characterization of the myocardium. Gated FDG-PET has the potential to assist in optimizing management of this patient population.
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Fluorodesoxiglucosa F18 , Radiofármacos , Tomografía Computarizada de Emisión , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda , Anciano , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The relaxation rates of iron-oxide nanoparticles compartmentalized within cells were studied and found to satisfy predictions of the static dephasing (SD) regime theory. THP-1 cells in cell culture were loaded using two different iron-oxide nanoparticles (superparamagnetic iron-oxide (SPIO) and ultrasmall SPIO (USPIO)) with four different iron concentrations (0.05, 0.1, 0.2, and 0.3 mg/ml) and for five different incubation times (6, 12, 24, 36, and 48 hr). Cellular iron-oxide uptake was assessed using a newly developed imaging version of MR susceptometry, and was found to be linear with both dose and incubation time. R(2)* sensitivity to iron-oxide loaded cells was found to be 70 times greater than for R(2), and 3100 times greater than for R(1). This differs greatly from uniformly distributed nanoparticles and is consistent with a cellular bulk magnetic susceptibility (BMS) relaxation mechanism. The cellular magnetic moment was large enough that R(2)' relaxivity agreed closely with SD regime theory predictions for all cell samples tested [R(2)'=2 pi/(9 x the square root of 3) x gamma LMD] where the local magnetic dose (LMD) is the sample magnetization due to the presence of iron-oxide particles). Uniform suspensions of SPIO and USPIO produced R(2)' relaxivities that were a factor of 3 and 8 less, respectively, than SD regime theory predictions. These results are consistent with theoretical estimates of the required mass of iron per compartment needed to guarantee SD-regime-dominant relaxivity. For cellular samples, R(2) was shown to be dependent on both the concentration and distribution of iron-oxide particles, while R(2)' was sensitive to iron-oxide concentration alone. This work is an important first step in quantifying cellular iron content and ultimately mapping the density of a targeted cell population.
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Compuestos Férricos/análisis , Espectroscopía de Resonancia Magnética , Compartimento Celular , Modelos Teóricos , Nanotecnología , Células Tumorales CultivadasRESUMEN
The rapid increase in body mass that often occurs following creatine (Cr) supplementation is believed to be due to intracellular water retention. The purpose of this study was to determine whether Cr consumption alters the magnetic resonance (MR) transverse relaxation (T(2)) distribution of skeletal muscle. Transverse relaxation can be used to model water compartments within a cell or tissue. In this double-blind study, subjects were asked to supplement their normal diet with creatine monohydrate (20 g day(-1) for 5 days) mixed with a grape drink (Creatine group, n = 7), or the grape drink alone (Placebo group, n = 8). Phosphorous MR spectroscopy was used to determine the effectiveness of the supplementation protocol. Subjects that responded to the Cr supplementation (i.e. showed a > 5 % increase in the ratio of the levels of phosphocreatine (PCr) and ATP) were placed in the Creatine group. Both proton MR imaging and spectroscopy were used to acquire T(2) data, at 1.89 T, from the flexor digitorum profundus muscle of each subject before and after supplementation. Following the supplementation period, the Creatine group showed a gain in body mass (1.2 +/- 0.8 kg, P < 0.05, mean +/- S.D.), and an increase in PCr/ATP ratio (23.8 +/- 16.4 %, P < 0.001). Neither group showed any changes in intracellular pH or T(2) calculated from MR images. However, the spectroscopy data revealed at least three components (> 5 ms) at approximately 20, 40 and 125 ms in both groups. Only in the Creatine group was there an increase in the apparent proton concentration of the two shorter components combined (+5.0 +/- 4.7 %, P < 0.05). According to the cellular water compartment model, the changes observed in the shorter T(2) components are consistent with an increase in intracellular water.