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For the construction of metal-free magnetic resonance imaging (MRI) contrast agents, radical-based nanoparticles (RNPs) are promising materials because they allow the water-proton longitudinal rela...

PURPOSE: To investigate the correlations between cortical bone microstructural properties and total water proton density (TWPD) obtained from three-dimensional ultrashort echo time Cones (3D-UTE-Cones) magnetic resonance imaging techniques. MATERIALS AND METHODS: 135 cortical bone samples were harvested from human tibial and femoral midshafts of 37 donors (61±24 years old). Samples were scanned using 3D-UTE-Cones sequences on a clinical 3T MRI and on a high-resolution micro-computed tomography (μCT) scanner. TWPD was measured using 3D-UTE-Cones MR images. Average bone porosity, pore size, and bone mineral density (BMD) were measured from μCT images at 9 μm voxel size. Pearson’s correlation coefficients between TWPD and μCT-based measures were calculated. RESULTS: TWPD showed significant moderate correlation with both average bone porosity (R=0.66, p

Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.

Mechanical and microstructural evaluations of cortical bone using ultrashort echo time magnetic resonance imaging (UTE-MRI) have been performed increasingly in recent years. UTE-MRI acquires considerable signal from cortical bone and enables quantitative bone evaluations. Fitting bone apparent transverse magnetization (T2*) decay using a bicomponent model has been regularly performed to estimate bound water (BW) and pore water (PW) in the quantification of bone matrix and porosity, respectively. Human cortical bone possesses a considerable amount of fat, which appears as MRI T2* signal oscillation and can subsequently lead to BW overestimation when using a bicomponent model. Tricomponent T2* fitting model has been developed to improve BW and PW estimations by accounting for fat contribution in the MRI signal. This study aimed to investigate the correlations of microstructural and mechanical properties of human cortical bone with water pool fractions obtained from a tricomponent T2* model. 135 cortical bone strips (~4 × 2 × 40 mm3 ) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using ten sets of dual-echo 3D-UTE-Cones sequences (TE = 0.032-24.0 ms) on a 3 T MRI scanner for T2* fitting analyses. Average bone porosity and pore size were measured using microcomputed tomography (μCT) at 9 μm voxel size. Bone mechanical properties were measured using 4-point bending tests. Using a tricomponent model, bound water fraction (FracBW ) showed significant strong (R = 0.70, P < 0.01) and moderate (R = 0.58-0.62, P < 0.01) correlations with porosity and mechanical properties, respectively. Correlations of bone microstructural and mechanical properties with water pool fractions were higher for tricomponent model results compared with the bicomponent model. The tricomponent T2* fitting model is suggested as a useful technique for cortical bone evaluation where the MRI contribution of bone fat is accounted for.

Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R 1 , but evidence for between-site reproducibility of R 1 in small-animal MRI is lacking. Objective: To assess R 1 repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R 1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1–13 days. R 1 was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured. Results: CoV for day-to-day repeatability (N = 180 regions of interest) was 2.34% and for between-centre reproducibility (N = 9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R 1 -based MR biomarkers were found to be quite sensitive even to such small errors in R 1 , notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni 2+ in 2% agarose varied between 0.66 s −1 mM −1 at 3 T and 0.94 s −1 mM −1 at 11.7T. Interpretation: While several factors affect the reproducibility of R 1 -based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases exceptional efforts might be required to ensure R 1 -reproducibility.

Purpose To quantify pure chemical exchange-dependent saturation transfer (CEST) related amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signals in a rat glioma model and to investigate the mixed effects of water content and water T1 on APT and NOE imaging signals. Methods Eleven U87 tumor-bearing rats were scanned at 4.7 T. A relatively accurate mathematical approach, based on extrapolated semisolid magnetization-transfer reference signals, was used to remove the concurrent effects of direct water saturation and semisolid magnetization-transfer. Pure APT and NOE signals, in addition to the commonly used magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym (3.5ppm), were assessed. Results The measured APT signal intensity of the tumor (11.06%, much larger than the value reported in the literature) was the major contributor (approximately 80.6%) to the MTRasym (3.5ppm) contrast between the tumor and the contralateral brain region. Both the water content ([water proton]) and water T1 (T1w ) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTRasym (3.5ppm) signals and T1w /[water proton]. Conclusion The effect of increasing T1w on the CEST signal in the tumor was mostly eliminated by the effect of increasing water content, and the observed APT-weighted hyperintensity in the tumor should be dominated by the increased amide proton concentration. Magn Reson Med 77:855-863, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

In this mini review, magnetic resonance imaging (MRI) contrast agents based on lanthanideoxide (Ln2O3) nanoparticles are described. Ln2O3 (Ln = Gd, Dy, Ho, and Er) nanoparticles are paramagnetic, but show appreciable magnetic moments at room temperature and even at ultrasmall particle diameters. Among Ln2O3 nanoparticles, Gd2O3 nanoparticles show larger longitudinal water proton relaxivity (r1) values than Gd-chelates because of the large amount of Gd in the nanoparticle, and the other Ln2O3 nanoparticles (Ln = Dy, Ho, and Er) show appreciable transverse water proton relaxivity (r2) values. Therefore, Gd2O3 nanoparticles are potential T1 MRI contrast agents while the other Ln2O3 nanoparticles are potential T2 MRI contrast agents at high MR fields.

Although radiofrequency ablation has become a worldwide accepted curative therapy for the treatment of cardiac arrhythmias, there is still a lack of lesion monitoring during ablation procedure. Magnetic Resonance (MR) thermometry based on the water proton frequency could give relevant information on local tissue temperature increase but requires dealing with motion and susceptibility artifacts due to the cardiac and respiratory motion. A real-time framework that overcomes these difficulties is described in this paper. The proposed approaches address both inter-scan and inplane motion using a rapid MR-acquisition sequence coupled with a robust optical-flow registration of all incoming images. The strategy was found to be robust and suitable to follow the temperature evolution in 10 healthy volunteers under free breathing conditions with a temperature standard deviation of 2.2 °C in the cardiac muscle at an update rate of approximately 1 Hz. Since local temperature rises due to RF ablation can lead to T1 and T2 relaxation time local variations, and thus to errors in the image-based registration process, we also analyze the performance of the algorithm during radiofrequency ablation applied under well controlled experimental conditions (no respiratory motion and cardiac triggered) using an ex vivo perfused pig heart. Contact electrophysiological signals were recorded simultaneously with magnetic resonance imaging by combining hardware and software filtering. A working heart setup, specifically designed for this project, provided a relevant model to assess the quality of cardiac MR-thermometry.

Nanoparticles capable of accumulating in tumor tissues are promising materials for tumor imaging and therapy. In this study, two radical nanoparticles (RNPs), denoted as 1 and 2, composed of self-assembled ureabenzene derivatives possessing one or two amphiphilic side chains were demonstrated to be candidates for metal-free functional magnetic resonance imaging (MRI) contrast agents (CAs). Because of the self-assembly behavior of 1 and 2 in a saline solution, spherical RNPs of sizes ∼50–90 and ∼30–100 nm were detected. In a highly concentrated solution, RNP 1 showed considerably small water-proton relaxivity values (r1 and r2), whereas RNP 2 showed an r1 value that was around 5 times larger than that of RNP 1. These distinct r1 values might be caused by differences in the self-assembly behavior by a hydration or dehydration process. In vivo studies with RNP 2 demonstrated a slightly enhanced T1-weighted image in mice, suggesting that the RNPs can potentially be used as metal-free functional MRI CAs for T1...

At present, a large number of MRI techniques areperformed employing Gd(III) complexes to enhance theimage contrast by increasing the water proton relaxation ratein the body. Some representative advantages of employingthe Gd(III) ion come from their unique properties such ashigh magnetic moment and long electron spin relaxationtime.

In this mini review, magnetic resonance imaging (MRI) contrast agents based on lanthanideoxide (Ln2O3) nanoparticles are described. Ln2O3 (Ln = Gd, Dy, Ho, and Er) nanoparticles are paramagnetic, but show appreciable magnetic moments at room temperature and even at ultrasmall particle diameters. Among Ln2O3 nanoparticles, Gd2O3 nanoparticles show larger longitudinal water proton relaxivity (r1) values than Gd-chelates because of the large amount of Gd in the nanoparticle, and the other Ln2O3 nanoparticles (Ln = Dy, Ho, and Er) show appreciable transverse water proton relaxivity (r2) values. Therefore, Gd2O3 nanoparticles are potential T1 MRI contrast agents while the other Ln2O3 nanoparticles are potential T2 MRI contrast agents at high MR fields.

a b s t r a c t In pomegranate, black heart disease develops inside the fruit without affecting the rind. Visual inspec- tion is not effective for identification of black heart in pomegranate fruit because of the lack of external symptoms. It has been shown that the water proton T2 relaxation time is sensitive to cell compartmental- ization. Proton NMR relaxometry was used to investigate the water T2 relaxation distribution in infected and healthy pomegranate arils, and to obtain information that indicates tissue damage. Multi-exponential inversion of the T2 data of healthy arils gave three relaxation peaks, which correspond to different water compartments in tissue. In infected arils, the three relaxation components shifted to lower relaxation time and a new fast relaxation component appeared indicating there was water redistribution among cell compartments caused by the infection. The change in cell membrane integrity in arils was also inves- tigated with the aid of paramagnetic ions. T2-weighted fast spin echo images were acquired for healthy and pomegranates with black heart. Histogram features of images, including mean, median, mode, stan- dard deviation, skewness, and kurtosis, were examined using partial least square discriminant analysis (PLS-DA). The PLS-DA model based on histogram features of MR image showed 92% accuracy in detecting the presence of black heart in pomegranate fruit. The significant change in T2 relaxation distribution in arils after infection proved that T2 relaxation time is a good indicator of black heart in pomegranate. The T2 based MR imaging showed its potential as a nondestructive technique for black heart detection in pomegranate.

A powerful method, termed flow relaxography, allowing the practical and accurate determination of the water proton MR signal relaxation time distributions has been recently introduced with a phantom, having both flowing and non-flowing water. It was demonstrated that this method can discriminate the signals from the flowing and non-flowing spins, since flow affects the apparent T1 (T1*) value. In this report, it is demonstrated that this technique is effective also in the human leg in vivo. Flow relaxographic angiography is presented for the first time. This technique promises to accomplish the twin goals of flow studies in medical MRI, to display vascular anatomy and measure its blood flow rate, in the same image.

Magnetic resonance imaging thermometry has been introduced as a technique for measurement of temperature changes in cooling dead rats. Rat pelvic magnetic resonance images were acquired sequentially more than 2h after euthanasia by halothane overdose. A series of temperature difference maps in cooling dead rats was obtained with calculating imaging phase changes induced by the water proton frequency shift caused by temperature changes. Different cooling processes were monitored by the temperature difference maps in the rats. Magnetic resonance imaging thermometry applied in the study of laboratory animals could theoretically reproduce a variety of causes of death with different environmental conditions. Outcomes from experimental animal studies could be translated into a temperature-based time of death estimation in forensics.

Differentiating ring-enhancing lesions into intra-cerebral abscesses or necrotic tumours is often difficult orimpossible with contrast-enhanced computed tomography(CT) or conventional magnetic resonance imaging (MRI).Diffusion-weighted imaging (DWI), which provides infor-mation about water diffusion, is a valuable test used in anattempt to resolve this diagnostic dilemma. As a rule, allbrain abscesses are hyperintense on DWI, secondary torestricted diffusion, with corresponding low intensityon apparent diffusion coefficient (ADC) map images.Conversely, the necrotic components of cerebral tumoursshow reduced signal intensity on DWI and increased ADCvalues compared with normal brain parenchyma as in mostcases, water diffusion is not restricted. We present a case ofa cerebral lesion that had DWI and ADC features of a cere-bral abscess but was, in fact, a squamous cell cerebralmetastasis from a primary lung malignancy. We hypothe-size that relatively densely packed tumour cells with highnuclear-to-cytoplasm ratio, as seen at histology, may limitextra and intracellular water proton motion, respectively.Restricted proton motion leads to a reduction in the rate ofapparent diffusion and to a marked increase in signal ondiffusion-weighted images, thus mimicking an abscess.Additional methods for ensuring maximal accuracy in thedifferentiation of cerebral lesions through the use of MRspectroscopy are also discussed.

article i nfo We measured 20-MHz R1 and R2 water proton NMR relaxation rates in ultrahigh dilutions (range 5.43·10 ! 8 M- 5.43·10 ! 48 M) of histamine in water (Hist-W) and in saline (Hist-Sal), prepared by iterative centesimal dilutions under vigorous agitation in controlled atmospheric conditions. Water and saline were similarly and simultaneously treated, as controls. The samples were immediately sealed in the NMR tubes after preparation, and then code-labelled. Six independent series of preparations were performed, representing about 7000 blind measurements. R2 exhibited a very broad scatter of values in both native histamine dilutions and solvents. No variation in R1 and R2 was observed in the solvents submitted to the iterative dilution/agitation process. By contrast, histamine dilutions exhibited slightly higher R1 values than solvents at low dilution, followed by a slow progressive return to the values of the solvents at high dilution. Unexpectedly, histamine dilutions remained distinguishablefrom solventsuptoultrahighlevelsofdilution(beyond10 ! 20

A new magnetic resonance imaging contrast agent containing organophosphonate functional groups was synthesized in high yield by a simple synthesis procedure. This molecule exhibits much higher longitudinal water proton relaxivity (37.0 mM−1 s−1) than commercial Omniscan (Gd-DTPA BMA, 5.7 mM−1 s−1) at 0.35 T. Notably, the relaxivity is larger than that of carboxylated Gd@C82 (16.0 mM−1 s−1) under the same conditions, indicating that the functional groups have an important role on the image contrast enhancement. In addition, the introduction of phosphonate substituents may provide bone-targeting MRI contrast agents.

Diffusion tensor imaging (DTI) is a powerful MR imaging technique that can be used to probe the microstructural environment of highly anisotropic tissues such as peripheral nerves. DTI has been used predominantly in the central nervous system, and its application in the peripheral nervous system does pose some challenges related to imaging artifacts, the small caliber of peripheral nerves, and low water proton density. However advances in MRI hardware and software have made it possible to use the technique in the peripheral nervous system and to obtain functional data relating to the effect of pathologic processes on peripheral nerves. This article reviews the imaging principles behind DTI and examines the literature regarding its application in assessing peripheral nerves.

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT) and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26–38 s−1mM−1 and r2/r1 = 1.4–1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Contains fulltext : 50751.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The characterization of tumor vasculature is essential in studying tumor physiology. The aim of this study was to develop a new method - based on water proton MR density measurements, in combination with ultrasmall superparamagnetic iron oxide (USPIO) administration - to measure absolute blood volume (BV) in murine colon carcinoma. MATERIALS AND METHODS: MRI experiments were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon carcinoma in six mice before and after administration of an USPIO blood-pool contrast agent. Density maps were obtained from the signal amplitude at TE=0 of the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO density maps to quantitatively yield absolute tumor BV maps. In a separate group of mice (n=6), the relative vascular area (RVA) of tumors was determined by immunohistochemistry. RESULTS: Ultrasmall superparamagnetic iron oxide administration resulted in a small decrease in the water proton MR density. The BV averaged over the six tumors was 4.6+/-1.6%. The value of the RVA measured by immunohistochemical staining was equal to 3.9+/-2.2%. CONCLUSIONS: After administration of an USPIO blood-pool agent (T(2) relaxivity > 100 mM(-1) s(-1)), the blood water protons become MRI invisible, and pixel-by-pixel BV map can be obtained by subtracting the calculated post-USPIO density map from the pre-USPIO density map. The value of absolute BV obtained with this novel MR approach is in good agreement with the value of the relative vascular measured by immunohistochemical staining.

In a recent series of studies (see, for example, Stroman et al. Magn Reson Imag 2001; 19:827-831), an increase of water proton density has been suggested to correlate with neuronal activity. Owing to the significant implications of such a mechanism for other functional experiments, the functional signal changes in humans at very short echo times were re-examined by spin-echo EPI at 3 T. The results do not confirm the previous hypothesis of a significant increase in extravascular proton density at TE = 0. Instead, an alternative explanation of the effect is offered: The use of a low threshold to identify activated voxels may generate an artificial offset in functional contrast due to the inclusion of false-positives in the analysis.

Diffusion-tensor imaging (DTI) non-invasively provides maps of microscopic structural information of oriented tissue in vivo, which is finding utility in studies of the aging population. In contrast to the white matter maturation process, investigators have observed significant declines in the white matter ordering in normal as well as in abnormal aging. These studies suggest that water proton non-random, anisotropic diffusion measured by DTI is highly sensitive to otherwise subtle disease processes not normally seen with conventional MRI tissue contrast mechanisms.

The water proton chemical shift observed in magnetic resonance is a measure of internal body temperature. The phase mapping method using this parameter has yielded a practical tool of non-invasive temperature imaging for monitoring thermal therapies, although the temperature coefficient of this parameter is small (-0.01ppm /°C).

The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating ligand-size was investigated. Both r1 and r2 values decreased with increasing ligand-size. We attributed this to the ligand-size effect. In addition the effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR field.

Epimysial and intramuscular connective tissues from calf and cow muscle were studied by NMR and DSC. Water proton NMR transverse relaxation times ( T 2 ) were measured at 10°C for both native and thermally-denatured at 90°C for 30–360 min. DSC measurements were used to determine the temperature and the variation enthalpy of sol→gel transition. According to the heating time, significant differences were observed between tissues. NMR discriminated the type of collagen whereas DSC distinguished the age of tissue. Differences were related to the degree of protein hydration, emphasising the complementary information from these two analytical tools.

Objective: To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise. Methods: A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM. Results: A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N. Conclusions: Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.

Previously we suggested a method for indirect detection of H217O via a combination of 1H spin–echo sequence and 17O decoupling. The method is based on the shortening of the water proton T2 due to the residual spin–spin coupling with the 17O nucleus, and on our finding that this shortening is abolished by applying an radio frequency field at the 17O resonance frequency. In the present work we demonstrate how the method can be used for imaging low concentrations of H217O, and report for the first time an application of this method to in vivo detection of H217O in live newborn mice, where the H217O was introduced either directly i.p. or by inhalation of 17O2 where it was formed by oxidative metabolic activity. © 1997 John Wiley & Sons, Ltd.

Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals used widely in MRI examinations. Gadolinium-based MRI contrast agents (GBCAs) are by far the most commonly used. To date, nine GBCAs have been commercialized for clinical use, primarily indicated in the central nervous system, vasculature, and whole body. GBCAs primarily lower the T(1) in vivo to create higher signal in T(1)-weighted MRI scans where GBCAs are concentrated. GBCAs are unique among pharmaceuticals, being water proton relaxation catalysts whose effectiveness is characterized by a rate constant known as relaxivity. The relaxivity of each GBCAs depends on a variety of factors that are discussed in terms of both the existing agents and future molecular imaging agents under study by current researchers. Current GBCAs can be divided into four different structural types (macrocyclic, linear, ionic, and nonionic) based on the chemistry of the chelating ligands whose primary purpose is to protect the body from dissociation of the relatively toxic Gd(3+) ion from the ligand. This article discusses how the chemical structure influences inherent and in vivo stability toward dissociation, and how it affects important formulation properties. Although GBCAs have a lower rate of serious adverse events than iodinated contrast agents, they still present some risk.

Mn(III)-loaded apoferritin is promptly reduced to Mn(II)–apoferritin by the oxidation of L-DOPA to melanin. The process is nicely witnessed by a marked relaxation enhancement of water proton relaxation rate that has been detected both in cultured melanoma cells and in tumor animal models.

Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors have been mostly performed using gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) contrast-enhanced imaging, which relies on Gd-DTPA leakage from hyperpermeable tumor vessels and subsequent accumulation in the tumor interstitium. In certain tumor types, especially diffuse glioma in the brain, incorporated tumor vessels are not necessarily leaky, complicating effective diagnosis via Gd-DTPA contrast-enhanced MRI. Another class of contrast agents, based on superparamagnetic ultrasmall iron oxide particles (USPIO), allows for non-invasive assessment of vascular volume within the tumor. Vascular volume can be obtained by calculating the change in water proton transverse relaxation rate (R (2) or R (2)) following USPIO administration. This allows for an objective comparison between vascular volumes of different tumors and also allows to perform longitudinal studies in order to assess, for example, treatment efficacy. Moreover, since the USPIO T (2) relaxivity is up to 20 times that of Gd-DTPA, USPIO provides a highly sensitive marker for alterations in vascular volume among tissues; this characteristic might be exploited for tumor detection. Thus, USPIO imaging may be a very attractive alternative to the most commonly used Gd-DTPA imaging and will at least have added value, especially for detection and delineation of diffuse infiltrative brain tumors.

BACKGROUND: Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data. PRINCIPAL FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T(2) and T(1rho), but did not change high-field T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T(1rho) to T(1).

The objective of this study is to assess whether ultrasmall superparamagnetic iron oxide (USPIO)-induced changes of the water proton longitudinal relaxation rate (R 1) provide a means to assess blood hemodynamics of tumors. Two types of murine colon tumors (C26a and C38) were investigated prior to and following administration of USPIO blood-pool contrast agent with fast R 1 measurements. In a subpopulation of mice, R 1 was measured following administration of hydralazine, a well-known blood hemodynamic modifier. USPIO-induced R 1 increase in C38 tumors (ΔR 1 = 0.072 ± 0.0081 s−1) was significantly larger than in C26a tumors (ΔR 1 = 0.032 ± 0.0018 s−1, N = 9, t test, P

The relaxation times (T1 and T2) of water proton in nuclear magnetic resonance (NMR) were measured with solutions containing bovine fibrinogen (Fbg), fibrin degradation products (FDP) and with fibrin-gel (Gel), at varying protein concentrations (0.7-70 mg/ml). Both T1 and T2 declined exponentially with increasing protein concentration. At a protein concentration of 35 mg/ml, the T1 of Fbg, Gel and FDP were 2.32, 2.12 and 2.82 s and the T2 values were 0.35, 0.17 and 0.70, respectively. The relaxation times for the control samples (0.2 M borate buffer) were 3.41 (T1) and 2.28 (T2). When the relaxation rates (the inverse of T1 and T2), R1 and R2 were plotted against the protein concentration, there were positive linear correlations between them. Using the slopes of the plots, the hydration value of each protein was calculated. The hydration value (g of H2O/g of protein) was 0.24 for Fbg, 0.34 for Gel and 0.14 for FDP.

The 3-D, in vivo temperature distributions within tumor-bearing rats were measured using Magnetic Resonance Imaging (MRI) technique. The in vivo thermal distributions of rats were measured using MRI chemical shift of water proton density. DMBA-4 tumor bearing rats are treated using laser photothermal therapy combined with immunoadjuvant under the observation of MRI. The thermal images and the immunological responses were studied and their relationships were investigated. The study of thermal distribution and correlation with the immunological response under laser treatment provided rich information with potential guidance for thermal-immunological therapy.

With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or “gadofullerenes” are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivo T 1 -weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

Magnetization transfer (MT) imaging provides a unique method of tissue characterization by capitalizing on the interaction between solid-like tissue components and bulk water. We used a continuous-wave (CW) MT pulse sequence with low irradiation power to study healthy human brains in vivo at 3 T and quantified the asymmetry of the MT effects with respect to the water proton frequency. This asymmetry was found to be a difference of approximately a few percent from the water signal intensity, depending on both the RF irradiation power and the frequency offset. The experimental results could be quantitatively described by a modified two-pool MT model extended with a shift contribution for the semisolid pool with respect to water. For white matter, this shift was fitted to be 2.34 +/- 0.17 ppm (N = 5) upfield from the water signal.

International audience; Local thermal therapies are increasingly used in the clinic for tissue ablation. During energy deposition, the actual tissue temperature is difficult to estimate since physiological processes may modify local heat conduction and energy absorption. Blood flow may increase during temperature increase and thus change heat conduction. In order to improve the therapeutic efficiency and the safety of the intervention, mapping of temperature and thermal dose appear to offer the best strategy to optimize such interventions and to provide therapy endpoints. MRI can be used to monitor local temperature changes during thermal therapies. On-line availability of dynamic temperature mapping allows prediction of tissue death during the intervention based on semi-empirical thermal dose calculations. Much progress has been made recently in MR thermometry research, and some applications are appearing in the clinic. In this paper, the principles of MRI temperature mapping are described with special emphasis on methods employing the temperature dependency of the water proton resonance frequency. Then, the prospects and requirements for widespread applications of MR thermometry in the clinic are evaluated.

Over the last several years, great interest has developed in the potential use of carbon nanostructures (C60 fullerenes and nanotubes) in medicine. In some cases, medical agents derived from these materials have demonstrated greater efficacy than existing clinical agents in many imaging and therapeutic applications. This chapter provides an overall review of the application of these materials in the area of magnetic resonance imaging (MRI), with an emphasis on their future applications in targeted MR molecular imaging for the early detection of cancer and other life-threatening diseases.

Diffusion-weighted MR imaging has great potential in studies of experimental brain research. Heavy diffusion-weighting is useful in determining the presence of anisotropic water proton diffusion in myelinated white matter structures in cat brain and spine. Large differences in apparent diffusion rates are observed between white matter tissues compared to gray, which does not displayed anisotropy. However, large decreases in apparent diffusion rates are observed in gray matter following experimentally-induced cerebral ischemia. This change in diffusion behavior is apparent within minutes upon ischemic onset and can be reversed upon reperfusion. Motion artifacts, often severe in spin-echo diffusion studies requiring 10-20 minutes to perform, can be largely eliminated by echoplanar, high-speed (150 msec) diffusion experiments.

Publisher Summary This chapter describes the magnetic resonance imaging (MRI) in animal models of pathologies. MRI is a well-recognized tool for in vivo characterization of animal models of human pathologies in preclinical research. It is found that because of its noninvasiveness, high soft contrast, and high space resolution, which can reach 50–100 μm in small laboratory animals, MRI constitutes a powerful morphologic technique. MR signal is sensitive to a number of parameters, including proton density, water proton relaxation times microscopic water self-diffusion, and macroscopic flow. The signal intensities were obtained by the region-of-interest (ROI) analysis. Five transversal contiguous slices were selected across the lesion with the criterion to cover the whole thigh. An operator-defined ROI was manually traced on the muscle of both the infected and the normal leg, avoiding the bone, as well as the subcutaneous edema, which appears strongly hyperintense. The use of localized spectroscopy for characterizing in vivo brown adipose tissue in terms of its content of poly-unsaturated fatty acids is also elaborated.

PLoS one 9(3), e91620 (2014). doi:10.1371/journal.pone.0091620, Published by PLoS [u.a.], Lawrence, Kan.

For better understanding of the behavior of water molecules in the animal brain, changes in magnetic resonance water proton relaxation processes were studied in the rat during maturation. Midbrains of male Wistar rats were removed at various time points ranging from 2 to 70 days after birth. Changes in relaxation time (water proton longitudinal relaxation time by the inversion recovery, and water proton transverse relaxation time by the spin echo and the Carr-Purcell-Meiboom-Gill pulse sequence (CPMG)) and water content were then determined for various stages of brain development. During maturation both water proton longitudinal relaxation time and water proton transverse relaxation time values decreased and this finding paralleled the decline in water content. Using the CPMG pulse sequence, the transverse relaxation time values were observed to separate into two components after 21 days. Morphologically, the most prominent change at the matured stage of midbrain development in the rat is myelination. Water proton relaxation time, which can be estimated using the CPMG pulse sequence, showed a close correlation with myelination in the central nervous system.

The development of sensitive and noninvasive magnetic resonance (MR) techniques for the long- and short-term evaluation of vascular prostheses requires detailed knowledge of the evolutionary trend of the MR properties of the perigraft tissue during the healing process. To characterize changes in water MR properties, the water proton relaxation times, T1 and T2, of the muscle in the vicinity of an implanted polyester material were measured as a function of implantation time. To provide better insight into interpretation of the MR results, we carried out histologic and peripheral blood cell activation studies and tissue water content measurements. The MR results illustrated the sensitivity of the relaxation times to changes in cellular response to the presence of an implant. The evolutionary trend of these MR parameters exhibited two distinct phases. The crossover from phase I to phase II occurred around 10 days postimplantation. This crossover is attributed to the transition in the inflammatory response from the acute phase to the chronic phase. During the acute phase, the very high initial T1 and T2s (the slower relaxing component of the transverse relaxation time) values decreased significantly and steadily. The value of T1 dropped by a factor of 2, whereas T2s went down by a factor of 6. During the same time, the diffusion parameter, beta, remained constant. However, during the chronic phase, the diffusion parameter increased sharply. By 30 days postimplantation, the value of beta had increased by a factor of 10. The relaxation times, on the other hand, increased steadily with implantation time. Because the current MR results provide an in vivo and noninvasive follow-up of the healing process around the polyester implant material, they will be of considerable value in the early detection of vascular graft complications by MR imaging.

Microbial anionic polysaccharides, although structurally closely related, exhibit strikingly different gelling properties in aqueous media (physical gels formation). Experimental observations are traced to differences, minor differences in some instances, in primary structures. Chemical gels have been prepared using deacylated gellan by means of an interchain partial esterification procedure, and a sample subjected to preliminary characterization in terms of swelling properties. NMR water proton relaxation data show that such amples display a remarkable water retention capability.

The goal of modern surgery is always to reduce the risks of surgery and anesthesia to a minimum. Our new method is carried out in local anesthesia, the surgical procedure is reduced to burrhole surgery and the procedure itself is real time controlled by the magnetic resonance tomography. The program allows the user to superpose at all times the isotherms to the recent MR picture with the brain tumor. The recent algorithm uses the water proton chemical shift. It possesses both a high sensitivity and a tissue independent effect and it also leads to an excellent method of monitoring temperature changes.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The design, relative merits, and initial applications of targeted relaxation enhancement agents, a new form of MRI contrast media, are briefly discussed. These agents are designed to bind reversibly to target macromolecules in a tissue of interest, thus enhancing water proton relaxation efficiency and MRI contrast. Initial applications for targeted agents include blood pool and hepatobiliary imaging.

1H Magnetic resonance imaging (MRI) was used to study the effects of photodynamic therapy (PDT) on normal rat brain (n = 5) using T1-, T2-, diffusion-, and proton density (rho)-weighted images. Rats received intraperitoneal injections of 12.5 mg/kg of Photofrin II, and 48 hours later the dural area over the frontal cortex was treated with 35 J/cm2 of light (632 +/- 1 nm). The T1-, T2-, and diffusion-weighted images revealed an evolving high contrast region of brain that corresponded to the PDT-treated area. Lesioned brain exhibited significant increases in T1 and T2 relaxation times at 1 day (P less than 0.01) and 3 days (T1, P = 0.018; T2, P less than 0.01) after treatment, compared with the contralateral equivalent volume of nonlesioned brain. Water proton diffusion coefficient (DW) in the lesioned area decreased at 1 day (P = 0.026) and increased at 3 days (P = 0.012) compared with nonlesioned brain. An increase in the proton density ratio (rho D/rho O) from PDT (rho D) versus nonlesioned side (rho O) was found 3 days after PDT treatment (P = 0.03). The data indicate that the biophysical parameters obtained from magnetic resonance imaging scans, T1, T2, DW, and proton density, can be used to monitor changes in an evolving photochemically induced lesion.

A measurement protocol providing a correct adjustment of the irradiation frequencies for well separated fat and water images of the lumbar spine is presented. To determine accurately the Larmor frequencies of water and fat protons within the vertebral bodies, a volume selective spectrum of a volume element (13 mm)3 located in a lumbar vertebral body was acquired with the 90 degrees-180 degrees-180 degrees double spin-echo method. These Larmor frequencies are used to adjust the frequency-selective pulse of the SENEX chemical-shift imaging sequence. This procedure provides well separated fat and water images for a large field of view even in the inhomogeneous region of the vertebral column. Their clinical importance is demonstrated by localized Larmor frequency-guided (LLFG) SENEX 1H images of the lumbar spine in healthy persons of different age and in a patient with acute myeloid leukemia.