Spin Relaxation Of Water Protons Research Articles

Biotin‐Conjugated Poly(Acrylic Acid)‐Grafted Ultrasmall Gadolinium Oxide Nanoparticles for Enhanced Tumor Imaging

AbstractHerein, biotin (Bio)‐conjugated poly(acrylic acid) (PAA)‐grafted ultrasmall gadolinium oxide nanoparticles (Bio‐PAA‐Gd2O3 NPs) were synthesized for enhanced tumor imaging using Bio as a tumor‐targeting ligand. The average particle diameter of Gd2O3 NPs was 2.1 nm. The Bio‐PAA‐Gd2O3 NPs exhibited excellent colloidal stability (i. e., no precipitation) and a high longitudinal water proton spin relaxivity (r1) of 23.8 s−1 mM−1 (r2/r1=1.6 and r2=transverse water proton spin relaxivity), which was ∼6 times higher than those of commercial Gd‐chelated magnetic resonance imaging (MRI) contrast agents. Cytotoxicity tests using two cell lines showed that the Bio‐PAA‐Gd2O3 NPs were almost non‐toxic up to the measured concentration of 500 μM Gd. The enhanced tumor imaging of the Bio‐PAA‐Gd2O3 NPs was demonstrated through their higher positive contrasts and longer contrast retention at the tumor after intravenous injection in T1 MR images, compared with those of the control PAA‐Gd2O3 NPs.

Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s−1mM−1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.

New Class of Efficient T2 Magnetic Resonance Imaging Contrast Agent: Carbon-Coated Paramagnetic Dysprosium Oxide Nanoparticles.

Nanoparticles are considered potential candidates for a new class of magnetic resonance imaging (MRI) contrast agents. Negative MRI contrast agents require high magnetic moments. However, if nanoparticles can exclusively induce transverse water proton spin relaxation with negligible induction of longitudinal water proton spin relaxation, they may provide negative contrast MR images despite having low magnetic moments, thus acting as an efficient T2 MRI contrast agent. In this study, carbon-coated paramagnetic dysprosium oxide (DYO@C) nanoparticles (core = DYO = DyxOy; shell = carbon) were synthesized to explore their potential as an efficient T2 MRI contrast agent at 3.0 T MR field. Since the core DYO nanoparticles have an appreciable (but not high) magnetic moment that arises from fast 4f-electrons of Dy(III) (6H15/2), the DYO@C nanoparticles exhibited an appreciable transverse water proton spin relaxivity (r2) with a negligible longitudinal water proton spin relaxivity (r1). Consequently, they acted as a very efficient T2 MRI contrast agent, as proven from negative contrast enhancements seen in the in vivo T2 MR images.

A Novel Paramagnetic Nanoparticle T2 Magnetic Resonance Imaging Contrast Agent With High Colloidal Stability: Polyacrylic Acid‐Coated Ultrafine Dysprosium Oxide Nanoparticles

Until now, there have been limited studies on T2 magnetic resonance imaging (MRI) contrast agents (CAs) using paramagnetic nanoparticles (NPs). In this study, ultrafine dysprosium oxide (Dy2O3) NPs were synthesized as a T2 MRI CA. To obtain high biocompatibility and colloidal stability in aqueous medium for in vivo applications, they were grafted with polyacrylic acid. They displayed paramagnetism with an appreciable magnetization value at 300 K and consequently, an appreciable transverse water proton spin relaxivity (r2) value which increased as the applied MR field increased. Their potential as a T2 MRI CA was proved by taking in vivo T2 MR images in mice.

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles.

The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s−1mM−1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

Carbazole as Linker for Dinuclear Gadolinium‐Based MRI Contrast Agents

Ligands able to complex two gadolinium ions have been synthesized and characterized in view of the ability of the complexes to increase the spin relaxation of water protons. All ligands are based on the heptadentate diethylenetriaminetetraacetic acid (DTTA) chelator and carbazole as a rigid linker. Depending on the derivatization on the nitrogen atom of the five‐membered ring, the compounds form small aggregates in aqueous solution, self‐assemble to form micelles or bind to human serum albumin. In all cases, this leads to a marked increase in 1H relaxivity at nuclear Larmor frequencies between 20 and 60 MHz. Water exchange on the gadolinium ions as measured by 17O NMR relaxation is fast enough not to limit relaxivity. 1H nuclear magnetic relaxation dispersion profiles were also measured and analyzed using Solomon–Bloembergen–Morgan theory including Lipari–Szabo treatment to include internal motion or anisotropic rotation.

Nuclear magnetic relaxation by the dipolar EMOR mechanism: Multi-spin systems.

In aqueous systems with immobilized macromolecules, including biological tissues, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. Starting from the stochastic Liouville equation, we have previously developed a rigorous EMOR relaxation theory for dipole-coupled two-spin and three-spin systems. Here, we extend the stochastic Liouville theory to four-spin systems and use these exact results as a guide for constructing an approximate multi-spin theory, valid for spin systems of arbitrary size. This so-called generalized stochastic Redfield equation (GSRE) theory includes the effects of longitudinal-transverse cross-mode relaxation, which gives rise to an inverted step in the relaxation dispersion profile, and coherent spin mode transfer among solid-like spins, which may be regarded as generalized spin diffusion. The GSRE theory is compared to an existing theory, based on the extended Solomon equations, which does not incorporate these phenomena. Relaxation dispersion profiles are computed from the GSRE theory for systems of up to 16 protons, taken from protein crystal structures. These profiles span the range from the motional narrowing limit, where the coherent mode transfer plays a major role, to the ultra-slow motion limit, where the zero-field rate is closely related to the strong-collision limit of the dipolar relaxation rate. Although a quantitative analysis of experimental data is beyond the scope of this work, it is clear from the magnitude of the predicted relaxation rate and the shape of the relaxation dispersion profile that the dipolar EMOR mechanism is the principal cause of water-1H low-field longitudinal relaxation in aqueous systems of immobilized macromolecules, including soft biological tissues. The relaxation theory developed here therefore provides a basis for molecular-level interpretation of endogenous soft-tissue image contrast obtained by the emerging low-field magnetic resonance imaging techniques.

Nuclear magnetic relaxation by the dipolar EMOR mechanism: Three-spin systems.

In aqueous systems with immobilized macromolecules, including biological tissue, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. Starting from the stochastic Liouville equation, we have developed a non-perturbative theory that can describe relaxation by the dipolar EMOR mechanism over the full range of exchange rates, dipole couplings, and Larmor frequencies. Here, we implement the general dipolar EMOR theory for a macromolecule-bound three-spin system, where one, two, or all three spins exchange with the bulk solution phase. In contrast to the previously studied two-spin system with a single dipole coupling, there are now three dipole couplings, so relaxation is affected by distinct correlations as well as by self-correlations. Moreover, relaxation can now couple the magnetizations with three-spin modes and, in the presence of a static dipole coupling, with two-spin modes. As a result of this complexity, three secondary dispersion steps with different physical origins can appear in the longitudinal relaxation dispersion profile, in addition to the primary dispersion step at the Larmor frequency matching the exchange rate. Furthermore, and in contrast to the two-spin system, longitudinal relaxation can be significantly affected by chemical shifts and by the odd-valued ("imaginary") part of the spectral density function. We anticipate that the detailed studies of two-spin and three-spin systems that have now been completed will provide the foundation for developing an approximate multi-spin dipolar EMOR theory sufficiently accurate and computationally efficient to allow quantitative molecular-level interpretation of frequency-dependent water-proton longitudinal relaxation data from biophysical model systems and soft biological tissue.

Nuclear magnetic relaxation by the dipolar EMOR mechanism: General theory with applications to two-spin systems.

In aqueous systems with immobilized macromolecules, including biological tissue, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. We have embarked on a systematic program to develop, from the stochastic Liouville equation, a general and rigorous theory that can describe relaxation by the dipolar EMOR mechanism over the full range of exchange rates, dipole coupling strengths, and Larmor frequencies. Here, we present a general theoretical framework applicable to spin systems of arbitrary size with symmetric or asymmetric exchange. So far, the dipolar EMOR theory is only available for a two-spin system with symmetric exchange. Asymmetric exchange, when the spin system is fragmented by the exchange, introduces new and unexpected phenomena. Notably, the anisotropic dipole couplings of non-exchanging spins break the axial symmetry in spin Liouville space, thereby opening up new relaxation channels in the locally anisotropic sites, including longitudinal-transverse cross relaxation. Such cross-mode relaxation operates only at low fields; at higher fields it becomes nonsecular, leading to an unusual inverted relaxation dispersion that splits the extreme-narrowing regime into two sub-regimes. The general dipolar EMOR theory is illustrated here by a detailed analysis of the asymmetric two-spin case, for which we present relaxation dispersion profiles over a wide range of conditions as well as analytical results for integral relaxation rates and time-dependent spin modes in the zero-field and motional-narrowing regimes. The general theoretical framework presented here will enable a quantitative analysis of frequency-dependent water-proton longitudinal relaxation in model systems with immobilized macromolecules and, ultimately, will provide a rigorous link between relaxation-based magnetic resonance image contrast and molecular parameters.

Anisotropy of spin relaxation of water protons in cartilage and tendon

Transverse spin relaxation rates of water protons in articular cartilage and tendon depend on the orientation of the tissue relative to the applied static magnetic field. This complicates the interpretation of magnetic resonance images of these tissues. At the same time, relaxation data can provide information about their organisation and microstructure. We present a theoretical analysis of the anisotropy of spin relaxation of water protons observed in fully hydrated cartilage. We demonstrate that the anisotropy of transverse relaxation is due almost entirely to intramolecular dipolar coupling modulated by a specific mode of slow molecular motion: the diffusion of water molecules in the hydration shell of a collagen fibre around the fibre, such that the molecular director remains perpendicular to the fibre. The theoretical anisotropy arising from this mechanism follows the 'magic-angle' dependence observed in magnetic-resonance measurements of cartilage and tendon and is in good agreement with the available experimental results. We discuss the implications of the theoretical findings for MRI of ordered collagenous tissues.

Dynamics of paramagnetic agents by off-resonance rotating frame technique in the presence of magnetization transfer effect

The simple method for measuring the rotational correlation time of paramagnetic ion chelates via off-resonance rotating frame technique is challenged in vivo by the magnetization transfer effect. A theoretical model for the spin relaxation of water protons in the presence of paramagnetic ion chelates and magnetization transfer effect is described. This model considers the competitive relaxations of water protons by the paramagnetic relaxation pathway and the magnetization transfer pathway. The influence of magnetization transfer on the total residual z-magnetization has been quantitatively evaluated in the context of the magnetization map and various difference magnetization profiles for the macromolecule conjugated Gd-DTPA in cross-linked protein gels. The numerical simulations and experimental validations confirm that the rotational correlation time for the paramagnetic ion chelates can be measured even in the presence of strong magnetization transfer. This spin relaxation model also provides novel approaches to enhance the detection sensitivity for paramagnetic labeling by suppressing the spin relaxations caused by the magnetization transfer. The inclusion of the magnetization transfer effect allows us to use the magnetization map as a simulation tool to design efficient paramagnetic labeling targeting at specific tissues, to design experiments running at low RF power depositions, and to optimize the sensitivity for detecting paramagnetic labeling. Thus, the presented method will be a very useful tool for the in vivo applications such as molecular imaging via paramagnetic labeling.

Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere

Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0–30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s−1 Gy−1, respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s−1 Gy−1 at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose–response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.

1H Spin–Spin Relaxation in Normal and Cataractous Human, Normal Fish and Bird Eye Lenses

A systematic study on nuclear spin–spin relaxation of water protons in human, fish and bird eye lenses/lens nuclei is reported. The purpose of this study is to clarify the real nature of the relaxation processes not describable as a single exponential decay. The characterization of the spin–spin relaxation by a single exponential is commonly used both in literature and in MRI diagnostics. However, in our opinion, this single exponential decay hypothesis is an oversimplification that can lead to the loss of essential information. Our measurements were performed by Carr–Purcell–Meiboom–Gill (CPMG) pulse sequences on human, carp, chicken and turkey eye lenses/lens nuclei. Several hundreds of CPMG echo amplitude were detected and the time-dependence of their decay was determined by careful fitting procedures. Our results clearly rule out the single exponential decay hypothesis for eye lenses: at least two or three decaying components are observed. These phenomena need further investigations: it should be decided which of the relaxation parameters, T2I-s and Ai-s gives the most characteristic physiological or pathological information. It is claimed that the amplitude ratio of the bound and the free water fraction carries the most characteristic information. During the cataract formation the weight of free water is raised by more than 25%.

Test of Electron Delocalization Effects on Water-Proton Spin-Lattice Relaxation by Bromination of [Tetrakis(4-sulfonatopheny)porphine]manganese.

The potential value of electron spin delocalization as a means for substantially increasing the ability of a paramagnetic metal complex to induce nuclear spin relaxation of water protons has been examined by covalent attachment of bromine atoms in the beta-pyrrole positions of the [5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine]manganese complexes[Mn(III)TPPS](3)(-) and [Mn(II)TPPS].(4)(-) The water-proton spin-lattice relaxivities are reported as a function of magnetic field strength for the brominated and nonbrominated metalloporphyrins over the range of magnetic field strengths corresponding to proton Larmor frequencies between 0.01 and 30 MHz. The brominated metalloporphyrins increase the water-proton relaxativities compared to the nonbrominated metalloporphrins, and, at low magnetic field strengths, the brominated [Mn(II)TPPS](4)(-) complex rivals the efficiency of the hexaaquomanganese(II) ion. Attempts to fit the experimental data to theories for paramagnetic relaxation, which are based on the point-dipole approximation, result in distances between the paramagnetic center and the water proton that are unreasonably short based on published structural data. The excess relaxivity implies that the point-dipole approximation may be inappropriate for these porphyrin systems and electron spin delocalization may provide a significant contribution to nuclear spin relaxation that may be fruitfully exploited in construction of contrast agents for magnetic resonance imaging.

NMR relaxation enhancement in gels polymerized and cross-linked by ionizing radiation: A new approach to 3D dosimetry by MRI

A new type of tissue-equivalent medium for magnetic resonance imaging of the dose distributions produced by ionizing radiation has been developed. Agarose gel is infused with acrylamide and N, N′-methylene-bis-acrylamide (Bis) comonomers, which are readily polymerized by free radical initiators in de-aerated aqueous solutions. Polymerization and cross-linking induced locally by free radical products of water radiolysis increase the rate of water proton spin relaxation gradually up to doses of about 15 Gy. The slopes of the dose-response curves at 64 MHz are 0.015 and 0.28 s −1 Gy −1 for R 1 and R 2, respectively. The agarose matrix as well as the high (50% by weight) relative concentration of the cross-linker (Bis) per total comonomer limit the spread of polymerization so that the spatial distribution of the radiation dose is faithfully represented in the resultant spatial distribution of relaxation rates. The gel can be imaged with conventional magnetic resonance imaging devices with high spatial resolution and accuracy. In addition, due to the well established effect of the precipitation of insoluble agglomerates of highly cross-linked acrylamide, the optical turbidity of the gel increases gradually with the absorbed dose. This may provide an additional means of visualizing the dose distribution in three dimensions. The major advantage of the acrylamide-Bis-agarose gels over those that depend on ionic chemical dosimeters, for example, Fricke-infused gels, lies in the lack of diffusion of radiation-induced chemical changes subsequent to or concurrent with irradiation.

Nuclear magnetic spin-lattice relaxation of water protons caused by metal cage compounds.

The nuclear magnetic spin-lattice relaxation rates of water protons are reported for solutions of manganese(II), copper(II), and chromium(III) cage complexes of the sarcophagine type. As simple aqueous solutions, the complexes are only modest magnetic relaxation agents, presumably because they lack protons on atoms in the first-coordination-sphere protons that are sufficiently labile to mix the large relaxation rate at the metal complex with that of the bulk solvent. The relaxation is approximately modeled using spectral density functions derived for translational diffusion of the interacting dipole moments with the modification that the electron spin relaxation rate is directly included as a contribution to the correlation time. In all cases studied, the electron spin relaxation rate is sufficiently large that it contributes directly to the water-proton spin relaxation process. The poor relaxation efficiency of the cage compound may, however, be improved dramatically by binding the complex to a protein. The efficiency is improved even further if the rotational motion of the protein is reduced drastically by an intermolecular cross-linking reaction. The relaxation efficiency of the cross-linked protein-cage complexes rivals that of the best first-coordination-sphere relaxation agents like [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]-.

Proton nuclear magnetic relaxation in aqueous copper(II) amine chelate solutions

Nuclear magnetic relaxation dispersion measurements are reported for aqueous solutions of copper(II) ion in solutions of ammonia, 1,2-diaminoethane and triethylenetetraamine. The water proton spin relaxation efficiency is increased dramatically over the hexaaquocopper(II) ion rate when square planar complexes are formed. The major factor contributing to this change is the development of a large hyperfine coupling between the coordinated amine protons and the copper(II) center that dominates low field relaxation rates. The relaxation is generally controlled by the rate of ligand exchange which is catalyzed by high ligand concentration. The triethylenetetraamine complex is substitutionally inert on the time scale of the nuclear spin relaxation and the water proton relaxation induced is dominated by the relative translational motion of the water and the metal center, i.e. outer sphere effects.

Origin of the nonexponentiality of the water proton spin relaxations in tissues

An attempt to explain the nonexponential recovery of the water proton spin magnetization in tissues is presented. The origin of this effect is the nonhomogeneity of the material and the distribution of slow diffusion correlation times. This proposal is based on a dispersion study of the tissue water proton spin relaxation time in the rotating frame.

Magnetic resonance studies of the mitochondrial divalent cation carrier

Measurements of water proton spin relaxation enhancements (ε) can be used to discriminate high-affinity binding of Mn 2+ or Gd 3+ to biological membranes, from low-affinity binding. In rat liver mitochondria, ε b values of approx. 11 are observed upon binding of Mn 2+ to the inner membrane, while internal or low-affinity binding remains invisible to this technique. Energy-driven Mn 2+ uptake by liver mitochondria results in the subsequent decay of ε ∗. Comparison of ε ∗ with the initial velocity of Mn 2+ uptake in rat liver mitochondria reveals a linear correlation, which holds at all temperatures between 0 °C and 40 °C, regardless of the mitochondrial protein concentration. Consequently, enhancement appears to reflect the binding of Mn 2+ to the divalent cation pump. Binding of Mn 2+ to blowfly flight muscle also results in substantial ε ∗, which is associated with the glycerol-1-phosphate dehydrogenase instead of divalent cation transport. Consequently, no decay in ε ∗ due to uptake occurs after Mn 2+ is bound. Lanthanide ions are also bound and transported by mitochondria. Addition of Gd 3+ to pigeon heart or rat liver mitochondria results in ε b ≈ 5–6, which decays with similar kinetics in both systems. The uptake velocity of Gd 3+ in rat liver mitochondria is about 1 6 the rate with which Mn 2+ is transported. Lanthanides also diminish ε ∗ due to the addition of Mn 2+, and greatly retard the Mn 2+ uptake kinetics. The presence of carbonylcyanide- p-trifluoromethoxyphenylhydrazone depresses ε ∗ upon addition of Mn 2+ or Gd 3+ and also uncouples energy-driven uptake. On the other hand, prolonged anaerobic incubation in the presence of antimycin and rotenone exhausts the mitochondria of their energy stores, blocks the uptake of Mn 2+, but does not affect ε ∗ significantly. Evidently, the uncoupler-induced disappearance of divalent cation binding sites is not the result of “de-energization”. Measurements of ε ∗ at several NMR frequencies indicate a correlation time ( τ b) for carrier-bound Mn 2+ in rat liver mitochondria between 20 ns and 4 ns as one varies the temperature between 10 °C and 30 °C. The 13 Kcal/mole activation energy for τ b suggests that the 11 ns time constant at room temperature represents the movement of the Mn II-carrier complex. On the other hand, τ b is probably approx. 100 times too short to represent the rotational motion of a carrier protein. Apparently, Mn 2+ binds to a small arm of the carrier which moves independently of the main body of any protein. In addition to Mn(H 2O) 6 2+, other complexes of Mn 2+ may also be bound and transported by rat liver mitochondria. Only a small increase in ε ∗ occurs upon addition of MnHPO 4, yet this species is accumulated by the mitochondria. Consequently, the carrier does not recognize divalent metal ions on the basis of charge.

Water Content and Proton Spin Relaxation Time for Malignant and Nonmalignant Tissues From Mice and Humans: Reply

Journal Article Water Content and Proton Spin Relaxation Time for Malignant and Nonmalignant Tissues From Mice and Humans: Reply Get access JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Page 626, https://doi.org/10.1093/jnci/52.6.626 Published: 01 February 1974