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؍‬ /(9 ͌ 3) ⅐ ␥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.Magn The macrophage is a white blood cell of the immune system that is intimately involved in the development and progression of inflammatory disease (1). Knowledge of the time course, spatial distribution, and magnitude of inflammatory response is critical for understanding disease progression (2), yet such information is difficult or even impossible to obtain from conventional histopathologic evaluation (3). Imaging methods that are capable of defining the extent of inflammatory activity in vivo would have a significant impact on inflammation research.It has recently become possible to visualize macrophage cells in vivo. New methods use iron-oxide nanoparticles to image cellular uptake and trafficking with MRI by exploiting the ability of certain cell types to ingest small particles in culture and in vivo through phagocytosis (4). For example, intravenously administered iron-oxide particles accumulate in macrophages of acute lesions in experimental autoimmune encephalomyelitis (5) and in tumor cells (6). While many studies have reported sensitivity to the presence of iron-oxide using T 1 (6,7), T 2 (5,8), and T * 2 (9,10) weighted imaging, methods quantifying the concentration of iron-oxide in vivo, as a first step towards characterizing ...

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The purpose of this study was to determine the effects of intense exercise on the proton transverse (T(2)) relaxation of human skeletal muscle. The flexor digitorium profundus muscles of 12 male subjects were studied by using magnetic resonance imaging (MRI; 6 echoes, 18-ms echo time) and in vivo magnetic resonance relaxometry (1,000 echoes, 1.2-ms echo time), before and after an intense handgrip exercise. MRI of resting muscle produced a single T(2) value of 32 ms that increased by 19% (P < 0.05) with exercise. In vivo relaxometry showed at least three T(2) components (>5 ms) for all subjects with mean values of 21, 40, and 137 ms and respective magnitudes of 34, 49, and 14% of the total magnetic resonance signal. These component magnitudes changed with exercise by -44% (P < 0.05), +52% (P < 0.05), and +23% (P < 0.05), respectively. These results demonstrate that intense exercise has a profound effect on the multicomponent T(2) relaxation of muscle. Changes in the magnitudes of all the T(2) components synergistically increase MRI T(2), but changes in the two shortest T(2) components predominate.