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 ...

MRI of superparamagnetic iron oxide (SPIO)-

Brain glucose hypometabolism has been observed in Alzheimer’s disease (AD) patients, and is detected with 18F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain β-amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain β-amyloid plaque deposition and 18FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain 18FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain 18FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial β-amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain 18FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

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