Bruce M. Moskowitz

Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells.

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 μg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24–39 s−1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for β-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

The effect of oxidation on the Verwey transition in magnetite

At the Verwey transition (Tv≈110–120 K), magnetite transforms from monoclinic to cubic spinel structure. It has long been believed that magnetic remanence and susceptibility would change markedly at Tv in the case of coarse grains but only slightly or inappreciably in the case of fine (<1 µm) grains. We find on the contrary that remanence changes at Tv by 50–80% in both large and small crystals, if they are stoichiometric. However, minor surface oxidation suppresses the transition, and the fact that fine grains oxidize more readily leads to an apparent size dependence. Our experiments used submicron magnetite cubes with mean sizes of 0.037, 0.076, 0.10 and 0.22 µm which were initially non-stoichiometric (oxidation parameter z from 0.2–0.7). A saturation isothermal remanent magnetization (SIRM) given in a 2.5 T field at 5 K decreased steadily during zero-field warming to 300 K with little or no indication of the Verwey transition. After the oxidized surface of each crystal was reduced to stoichiometric magnetite, the SIRM decreased sharply during warming by 50–80% around 110 K. The change in SIRM for the 0.22 µm grains was almost identical to that measured for a 1.5 mm natural magnetite crystal. Thus a 1012 change in particle volume does not materially affect the remanence transition at Tv but oxidation to z=0.3 essentially suppresses the transition. The effect of the degree of oxidation on Tv provides a sensitive test for maghemitization in soils, sediments and rocks.

Rock magnetic criteria for the detection of biogenic magnetite

Abstract We report results on the magnetic properties of magnetites produced by magnetotactic and dissimilatory iron-reducing bacteria. Magnetotactic bacterial (MTB) strains MS1, MV1 and MV2 and dissimilatory iron-reducing bacterium strain GS-15, grown in pure cultures, were used in this study. Our results suggest that a combination of room temperature coercivity analysis and low temperature remanence measurements provides a characteristic magnetic signature for intact chains of single domain (SD) particles of magnetite from MTBs. The most useful magnetic property measurements include: (1) acquisition and demagnetization of isothermal remanent magnetization (IRM) using static, pulse and alternating fields; (2) acquisition of anhysteretic remanent magnetization (ARM); and (3) thermal dependence of low temperature (20 K) saturation IRM after cooling in zero field (ZFC) or in a 2.5 T field (FC) from 300 K. However, potentially the most diagnostic magnetic parameter for magnetosome chain identification in bulk sediment samples is related to the difference between low temperature zero-field and field cooled SIRMs on warming through the Verwey transition (T ≈ 100 K). Intact chains of unoxidized magnetite magnetosomes have ratios of δFC/δZFC greater than 2, where the parameter δ is a measure of the amount of remanence lost by warming through the Verwey transition. Disruption of the chain structure or conversion of the magnetosomes to maghemite reduces the δFC/δZFC ratio to around 1, similar to values observed for some inorganic magnetite, maghemite, greigite and GS-15 particles. Numerical simulations of δFC/δZFC ratios for simple binary mixtures of magnetosome chains and inorganic magnetic fractions suggest that the δFC/δZFC parameter can be a sensitive indicator of biogenic magnetite in the form of intact chains of magnetite magnetosomes and can be a useful magnetic technique for identifying them in whole-sediment samples. The strength of our approach lies in the comparative ease and rapidity with which magnetic measurements can be made, compared to techniques such as electron microscopy.

LOW-TEMPERATURE MAGNETIC BEHAVIOR OF TITANOMAGNETITES

Titanium substitution has a significant effect on the temperature dependence (5–300 K) of low-temperature saturation remanence and of initial susceptibility in synthetic and natural titanomagnetite (Fe3−xTixO4, 0≤x 0.4, and electronic and lattice relaxation phenomena over the entire titanomagnetite compositional range. These features produce diagnostic magnetic behavior useful for titanomagnetite identification in natural samples. Moreover, the apparent similarities between the thermal decay of low-temperature remanence of titanomagnetite with pyrrhotite, pure magnetite, and superparamagnetic phases can lead to complications in interpreting low-temperature remanence data when titanomagnetite is present.

Changes in remanence, coercivity and domain state at low temperature in magnetite

Abstract Submicron magnetite crystals with mean sizes of 0.037, 0.10 and 0.22 μm undergo major changes in hysteresis properties and domain states in crossing the Verwey transition ( T V ≈120 K). The 0.037 μm crystals are single-domain (SD) both in the cubic phase at room temperature T 0 and in the monoclinic phase below T V . The 0.10 and 0.22 μm crystals have a mixture of SD and two-domain (2D) states at room temperature T 0 , but mainly SD structures below T V , in agreement with micromagnetic calculations. Coercive force H c increases on cooling through T V , by a factor 3–5 in the submicron magnetites and 40 in a 1.3 mm single crystal, because of the high crystalline anisotropy and magnetostriction of monoclinic magnetite. As a result, domain walls and SD moments are so effectively pinned below T V that all remanence variations in warming or cooling are reversible. However, between ≈100 K and T 0 , remanence behavior is variable. Saturation remanence (SIRM) produced in monoclinic magnetite at 5 K drops by 70–100% in warming across T V , with minor recovery in cooling back through T V (ultimate levels at 5 K of 23–37% for the submicron crystals and 3% for the 1.3 mm crystal). In contrast, SIRM produced in the cubic phase at 300 K decreases 5–35% (submicron) or >95% (1.3 mm) during cooling from 300 to 120 K due to continuous re-equilibration of domain walls, but there is little further change in cooling through T V itself. However, the submicron magnetites lose a further 5–15% of their remanence when reheated through T V . These irreversible changes in cycling across T V , and the amounts of the changes, have potential value in determining submicron magnetite grain sizes. The irreversibility is mainly caused by 2D→SD transformations on cooling through T V , which preserve or enhance remanence, while SD→2D transformations on warming through T V cause remanence to demagnetize.

Methods for estimating Curie temperatures of titanomaghemites from experimentalJs-T data

Abstract Methods for determining the Curie temperature ( T c ) of titanomaghemites from experimental saturation magnetization-temperature ( J s -T ) data are reviewed. J s -T curves for many submarine basalts and synthetic titanomaghemites are irreversible and determining Curie temperatures from these curves is not a straightforward procedure. Subsequently, differences of sometimes over 100°C in the values of T c may result just from the method of calculation. Two methods for determining T c will be discussed: (1) the graphical method, and (2) the extrapolation method. The graphical method is the most common method employed for determining Curie temperatures of submarine basalts and synthetic titanomaghemites. The extrapolation method based on the quantum mechanical and thermodynamic aspects of the temperature variation of saturation magnetization near T c , although not new to solid state physics, has not been used for estimating Curie temperatures of submarine basalts. The extrapolation method is more objective than the graphical method and uses the actual magnetization data in estimating T c .

Magnetic material in the human hippocampus

Magnetic analyses of hippocampal material from deceased normal and epileptic subjects, and from the surgically removed epileptogenic zone of a living patient have been carried out. All had magnetic characteristics similar to those reported for other parts of the brain [6]. These characteristics along with low temperature analysis indicate that the magnetic material is present in a wide range of grain sizes. The low temperature analysis also revealed the presence of magnetite through manifestation of its low temperature transition. The wide range of grain sizes is similar to magnetite produced extracellularly by the GS-15 strain of bacteria and unlike that found in magnetotactic bacteria MV-1, which has a restricted grain size range. Optical microscopy of slices revealed rare 5-10 micron clusters of finer opaque particles, which were demonstrated with Magnetic Force Microscopy to be magnetic. One of these was shown with EDAX to contain AI, Ca, Fe, and K, with approximate weight percentages of 55, 19, 19, and 5, respectively.

Unmixing magnetic assemblages and the magnetic behavior of bimodal mixtures

Stable single-domain (SSD) grains were mixed separately with superparamagnetic, pseudosingle-domain, and multidomain (MD) magnetite/maghemite particles in order to test the linearity of various magnetic parameters as a function of mixing ratio. Hysteresis loops, isothermal remanent magnetization acquisition curves, DC demagnetization curves, and low-temperature thermal demagnetization curves were measured on the mixtures. The experiments demonstrate that magnetization parameters are linearly dependent on the mixing ratio, while more complex parameters, e.g., coercivities, do not behave linearly as a function of mixing ratio. Armed with linearity, we apply a mathematical technique which, given a database of type curves, uses singular value decomposition to solve for the various concentrations of the magnetic phases in the mixture and a Monte Carlo simulation to determine the error in the inversion. We then test the technique on numerical mixtures, on the physical mixtures, and on a small set of natural samples from Lake Pepin, Minnesota. Finally, the magnetic behavior of the mixture of MD and SSD grains is considered, and two more mixture strains of MD and SSD grains (numerically produced) are considered to facilitate this discussion.

Relaxometry and magnetometry of the MR contrast agent MION-46L.

MION‐46L is an ultrasmall monocrystalline superparamagnetic (SPM) iron oxide that is of current interest as an MR contrast agent. It is believed to consist primarily of small maghemite or magnetite crystals that possess a SPM moment, but the exact magnetic properties and related mechanisms of T1 and T2 proton relaxation enhancement are not well understood. We have obtained a comprehensive data set consisting of magnetization curves, EPR spectra, and 1/T1 and 1/T2 nuclear magnetic relaxation dispersion (NMRD) profiles for this contrast agent. The magnetization curves show a primary curvature consistent with a SPM moment of 10,300 Bohr magnetons (BM) per particle. In addition, there is a secondary high‐field curvature that is consistent with a smaller SPM moment of 1600 BM, which may be responsible for the observed high‐field increase in 1/T2. Finally, there appear to be a considerable number of paramagnetic ions present that are needed to account for the high‐field increase in magnetization, and that can provide an alternative explanation for the magnitude of the low‐field T1 plateau. This “three‐phase model” appears to be successful in explaining in a self‐consistent and quantitative manner the combined results of the magnetometry, relaxometry, and EPR studies. Magn Reson Med 42:379–384, 1999. Published 1999 Wiley‐Liss, Inc.

Field-dependence of AC susceptibility in titanomagnetites

Abstract AC susceptibility measurements as a function of field amplitude Hac and of frequency show a strong field dependence for a set of synthetic titanomagnetites (Fe3−xTixO4) and for certain basalts from the SOH-1 Hawaiian drill hole and from Iceland. In-phase susceptibility is constant below fields of about 10–100 A/m, and then increases by as much as a factor of two as Hac is increased to 2000 A/m. Both the initial field-independent susceptibilities and the field-dependence of susceptibility are systematically related to composition: initial susceptibility is 3 SI for a single-crystal sphere of TM0 (x=0) and decreases with increasing titanium content; field-dependence is nearly zero for TM0 and increases systematically to a maximum near TM60 (x=0.6). This field dependence can in some cases be mistaken for frequency dependence, and lead to incorrect interpretations of magnetic grain size and composition when titanomagnetite is present.