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For the quantification of rotating frame relaxation times, the T 2ρ relaxation pathway plays an essential role. Nevertheless, T 2ρ imaging has been studied only to a small extent compared with T 1ρ , and preparation techniques for T 2ρ have so far been adapted from T 1ρ methods. In this work, two different preparation concepts are compared specifically for the use of T 2ρ mapping. The first approach involves transferring the balanced spin-locking (B-SL) concept of T 1ρ imaging. The second and newly proposed approach is a continuous-wave Malcolm-Levitt (CW-MLEV) pulse train with zero echo times and was motivated from T 2 preparation strategies. The modules are tested in Bloch simulations for their intrinsic sensitivity to field inhomogeneities and validated in phantom experiments. In addition, myocardial T 2ρ mapping was performed in mice as an exemplary application. Our results demonstrate that the CW-MLEV approach provides superior robustness and thus suggest that established methods of T 1ρ imaging are not best suited for T 2ρ experiments. In the presence of field inhomogeneities, the simulations indicated an increased banding compensation by a factor of 4.1 compared with B-SL. Quantification of left ventricular T 2ρ time in mice yielded more consistent results, and values in the range of 59.2-61.1 ms (R 2  = 0.986-0.992) were observed at 7 T., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range., Methods: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields. The REX detection approach was validated under controlled conditions in phantom experiments at 3 T. Gaussian and sinc-shaped stimuli were investigated. In addition, the detection of artificial fields resembling a cardiac QRS complex, which is the most prominent peak visible on a magnetocardiogram, was tested., Results: Bloch simulations demonstrated that the REX method has a high sensitivity to pulsed fields in the resonance case, which is met when the spin-lock frequency coincides with a non-zero Fourier component of the stimulus field. In the experiments, we found that magnetic stimuli of different durations and waveforms can be distinguished by their characteristic REX response spectrum. The detected REX amplitude was proportional to the stimulus peak amplitude (R 2  > 0.98) and the lowest field detection was 1 nT. Furthermore, the detection of QRS-like fields with varying QRS durations yielded significant results in a phantom setup (p < 0.001)., Conclusion: REX detection can be transferred to non-sinusoidal pulsed magnetic fields and could provide a non-invasive, quantitative tool for spatially resolved assessment of cardiac biomagnetism. Potential applications include the direct detection and characterization of cardiac conduction., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a randomized placebo-controlled clinical trial, we contrasted pain relief (3-month treatment period), and anatomical (gray matter density [GMD], assessed by voxel-based morphometry) and functional connectivity (resting state fMRI nodal degree count [DC]) adaptations, in 39 knee osteoarthritis (OA) patients (22 females), randomized to duloxetine (DLX, 60 mg once daily) or placebo. Pain relief was equivalent between treatment types. However, distinct circuitry (GMD and DC) could explain pain relief in each group: up to 85% of variance for placebo analgesia and 49% of variance for DLX analgesia. No behavioral measures (collected at entry into the study) could independently explain observed analgesia. Identified circuitry were outside of nociceptive circuitry and minimally overlapped with OA-abnormal or placebo response predictive brain regions. Mediation analysis revealed that changes in GMD and DC can influence each other across remote brain regions to explain observed analgesia. Therefore, we can conclude that distinct brain mechanisms underlie DLX and placebo analgesia in OA. The results demonstrate that even in the absence of differences in subjective pain relief, pharmacological treatments can be differentiated from placebo based on objective brain biomarkers. This is a crucial step to untangling mechanisms and advancing personalized therapy approaches for chronic pain., (© 2018 Wiley Periodicals, Inc.)

Purpose: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs., Methods: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T 1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T 1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference., Results: Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T 1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference., Conclusion: The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T 1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice., Methods: A flow-sensitive alternating inversion recovery arterial spin labeling method using an untriggered FLASH-read out with random sampling is used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism to reduce deviation from Look-Locker conditions are needed. Electrocardiogram and respiratory data are recorded for retrospective gating and triggering. A model-based technique is used to reconstruct missing k-space data to cope with the undersampling inherent in retrospectively gated methods. Acquisition and reconstruction were validated numerically and in phantom measurements before in vivo experimentation., Results: Quantitative perfusion maps were acquired within a single slice measurement time of 11 min. Perfusion values are in good accordance to literature values. Myocardial infarction could be clearly visualized and results were confirmed with histological results., Conclusion: The proposed method is capable of producing quantitative perfusion maps on arbitrary positions in the heart cycle within a short measurement time. The method is robust against irregular breathing patterns and heart rate changes and can be implemented on all scanners., (© 2014 Wiley Periodicals, Inc.)

Purpose: The quantification of myocardial perfusion using a Look-Locker flow-sensitive alternating inversion recovery- arterial spin labeling experiment is considered. Due to the anatomy of the heart, a substantial but unintended partial inversion of the inflowing blood occurs during the slice-selective inversion. Both, the partial inversion as well as the Look-Locker pulse train, influence the myocardial perfusion quantification and are addressed in this work., Methods: The mean relaxation time approximation is used to calculate the monoexponential relaxation time of the signal in perfused tissue under Look-Locker readout. The left ventricular blood serves as an approximation of the inflowing blood in the description of FAIR-ASL measurements with global and slice-selective inversion to correctly quantify the myocardial perfusion., Results: The analysis shows that the myocardial perfusion can be overestimated if the T1 -based quantification method is not adapted respecting the Look-Locker pulse train explicitly. Additionally, it turns out that without correction for the partial inversion of the blood pool during the slice-selective inversion the myocardial perfusion is underestimated., Conclusion: It is shown that the Look-Locker readout as well as the nonideal slice-selective inversion experiment have a considerable influence and have to be included properly to correctly quantify myocardial perfusion., (Copyright © 2013 Wiley Periodicals, Inc.)

There are serious concerns regarding safety when performing magnetic resonance imaging in patients with implanted conductive medical devices, such as cardiac pacemakers, and associated leads, as severe incidents have occurred in the past. In this study, several approaches for altering an implant's lead design were systematically developed and evaluated to enhance the safety of implanted medical devices in a magnetic resonance imaging environment. The individual impact of each design change on radiofrequency heating was then systematically investigated in functional lead prototypes at 1.5 T. Radiofrequency-induced heating could be successfully reduced by three basic changes in conventional pacemaker lead design: (1) increasing the lead tip area, (2) increasing the lead conductor resistance, and (3) increasing outer lead insulation conductivity. The findings show that radiofrequency energy pickup in magnetic resonance imaging can be reduced and, therefore, patient safety can be improved with dedicated construction changes according to a "safe by design" strategy. Incorporation of the described alterations into implantable medical devices such as pacemaker leads can be used to help achieve favorable risk-benefit-ratios when performing magnetic resonance imaging in the respective patient group., (Copyright © 2012 Wiley Periodicals, Inc.)

Determining the MR compatibility of medical implants and devices is becoming increasingly relevant. In most cases, the heating of conductive implants due to radiefrequency (RF) excitation pulses is measured by fluoroptic temperature sensors in relevant tests for approval. Another common method to determine these heating effects is MR thermometry using the proton resonance frequency. This method gives good results in homogeneous phantoms. However in many cases, technical shortcomings such as susceptibility artifacts prohibit exact proton resonance frequency thermometry near medical implants. Therefore, this work aimed at developing a fast T₁-based method which allows controlled MR-related heating of a medical implant while simultaneously quantifying the spatial and temporal temperature distribution. To this end, an inversion recovery snapshot Fast Low-Angle Shot (FLASH) sequence was modified with additional off-resonant heating pulses. With an accelerated imaging method and a sliding-window technique, every 7.6 s a new temperature map could be generated with a spatial in-plane resolution of 2 mm. The temperature deviation from calculated temperature values to reference fluoroptic probe was found to be smaller than 1 K., (Copyright © 2012 Wiley Periodicals, Inc.)

Aim: To investigate whether diagnostic data from implanted cardiac resynchronization therapy defibrillators (CRT-Ds) retrieved automatically at 24 h intervals via a Home Monitoring function can enable dynamic prediction of cardiovascular hospitalization and death., Methods and Results: Three hundred and seventy-seven heart failure patients received CRT-Ds with Home Monitoring option. Data on all deaths and hospitalizations due to cardiovascular reasons and Home Monitoring data were collected prospectively during 1-year follow-up to develop a predictive algorithm with a predefined specificity of 99.5%. Seven parameters were included in the algorithm: mean heart rate over 24 h, heart rate at rest, patient activity, frequency of ventricular extrasystoles, atrial-atrial intervals (heart rate variability), right ventricular pacing impedance, and painless shock impedance. The algorithm was developed using a 25-day monitoring window ending 3 days before hospitalization or death. While the retrospective sensitivities of the individual parameters ranged from 23.6 to 50.0%, the combination of all parameters was 65.4% sensitive in detecting cardiovascular hospitalizations and deaths with 99.5% specificity (corresponding to 1.83 false-positive detections per patient-year of follow-up). The estimated relative risk of an event was 7.15-fold higher after a positive predictor finding than after a negative predictor finding., Conclusion: We developed an automated algorithm for dynamic prediction of cardiovascular events in patients treated with CRT-D devices capable of daily transmission of their diagnostic data via Home Monitoring. This tool may increase patients' quality of life and reduce morbidity, mortality, and health economic burden, it now warrants prospective studies. ClinicalTrials.gov  NCT00376116.

Implanted medical devices such as cardiac pacemakers pose a potential hazard in magnetic resonance imaging. Electromagnetic fields have been shown to cause severe radio frequency-induced tissue heating in some cases. Imaging exclusion zones have been proposed as an instrument to reduce patient risk. The purpose of this study was to further assess the impact of the imaging landmark on the risk for unintended implant heating by measuring the radio frequency-induced electric fields in a body phantom under several imaging conditions at 1.5T. The results show that global radio frequency-induced coupling is highest with the torso centered along the superior-inferior direction of the transmit coil. The induced E-fields inside the body shift when changing body positioning, reducing both global and local radio frequency coupling if body and/or conductive implant are moved out from the transmit coil center along the z-direction. Adequate selection of magnetic resonance imaging landmark can significantly reduce potential hazards in patients with implanted medical devices., (© 2010 Wiley-Liss, Inc.)

This study reports the T(1) and T(2) relaxation rates of rhodamine-labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization. Therefore cells were incubated with rhodamine-labeled anionic magnetic nanoparticles and were prepared at decreasing concentrations. Additionally, rhodamine-labeled anionic magnetic nanoparticles in solution were used for extracellular measurements. T(1) and T(2) were determined at 7, 11.7, and 17.6 T. T(1) times were determined with an inversion-recovery snapshot-flash sequence. T(2) times were obtained from a multispin-echo sequence. Inductively coupled plasma-mass spectrometry was used to determine the iron content in all samples, and r(1) and r(2) were subsequently calculated. The results were then compared with cells labeled with AMI-25 and VSOP C-200. In solution, the r(1) and r(2) of rhodamine-labeled anionic magnetic nanoparticles were 4.78/379 (7 T), 3.28/389 (11.7 T), and 2.00/354 (17.6 T). In cells, the r(1) and r(2) were 0.21/56 (7 T), 0.19/37 (11.7 T), and 0.1/23 (17.6 T). This corresponded to an 11- to 23-fold decrease in r(1) and an 8- to 15-fold decrease in r(2) . A decrease in r(1) was observed for AMI-25 and VSOP C-200. AMI-25 and VSOP exhibited a 2- to 8-fold decrease in r(2) . In conclusion, cellular internalization of iron oxide nanoparticles strongly decreased their T(1) and T(2) potency., (Copyright © 2010 Wiley-Liss, Inc.)

Transgenic mouse models of human diseases have gained increasing importance in the pathophysiology of cardiovascular diseases (CVD). As an indirect measure of vascular stiffness, aortic pulse-wave velocity (PWV) is an important predictor of cardiovascular risk. This study presents an MRI approach that uses a flow area method to estimate local aortic pulse-wave velocity at different sites in the murine aorta. By simultaneously measuring the cross-sectional area and the through-plane velocity with a phase-contrast CINE method, it was possible to measure average values for the PWV in the ascending and descending aorta within the range of 2.4-4.3 m/s for C57BL/6J mice (ages 2 and 8 months) and apoE-knockout mice (age 8 months). Statistically significant differences of the mean values of the PWV of both groups could be determined. By repeating CINE measurements with a time delay of 1 ms between two subsequent data sets, an effective temporal resolution of 1000 frames/s (fps) could be achieved.

It had been previously shown that an idealized version of the two-wave-vector extension of the NMR pulsed-field-gradient spin echo diffusion experiment can be used to determine the apparent radius of geometries with restricted diffusion. In the present work, the feasibility of the experiment was demonstrated in an NMR imaging experiment, in which the apparent radius of axons in white matter tissue was determined. Moreover, numerical simulations have been carried out to determine the reliability of the results. For small diffusion times, the radius is systematically underestimated. Larger gradient area, finite length gradient pulses, and a statistical distribution of radii within a voxel all have a minor influence on the estimated radius.

Radiofrequency (RF)-related heating of cardiac pacemaker leads is a serious concern in magnetic resonance imaging (MRI). Recent investigations suggest such heating to be strongly dependent on an implant's position within the surrounding medium, but this issue is currently poorly understood. In this study, phantom measurements of the RF-induced electric currents inside a pacemaker lead were performed to investigate the impact of the device position and lead configuration on the amount of MRI-related heating at the lead tip. Seven hundred twenty device position/lead path configurations were investigated. The results show that certain configurations are associated with a highly increased risk to develop MRI-induced heating, whereas various configurations do not show any significant heating. It was possible to precisely infer implant heating on the basis of current intensity values measured inside a pacemaker lead. Device position and lead configuration relative to the surrounding medium are crucial to the amount of RF-induced heating in MRI. This indicates that a considerable number of implanted devices may incidentally not develop severe heating in MRI because of their specific configuration in the body. Small variations in configuration can, however, strongly increase the risk for such heating effects, meaning that hazardous situations might appear during MRI.

Conductive implants are in most cases a strict contraindication for MRI examinations, as RF pulses applied during the MRI measurement can lead to severe heating of the surrounding tissue. Understanding and mapping of these heating effects is therefore crucial for determining the circumstances under which patient examinations are safe. The use of fluoroptic probes is the standard procedure for monitoring these heating effects. However, the observed temperature increase is highly dependent on the positioning of such a probe, as it can only determine the temperature locally. Temperature mapping with MRI after RF heating can be used, but cooling effects during imaging lead to a significant underestimation of the heating effect. In this work, an MRI thermometry method was combined with an MRI heating sequence, allowing for temperature mapping during RF heating. This technique may provide new opportunities for implant safety investigations., ((c) 2008 Wiley-Liss, Inc.)

The purpose of this study was to assess the distribution of RF-induced E-fields inside a gel-filled phantom of the human head and torso and compare the results with the RF-induced temperature rise at the tip of a straight conductive implant, specifically examining the dependence of the temperature rise on the position of the implant inside the gel. MRI experiments were performed in two different 1.5T MR systems of the same manufacturer. E-field distribution inside the liquid was assessed using a custom measurement system. The temperature rise at the implant tip was measured in various implant positions and orientations using fluoroptic thermometry. The results show that local E-field strength in the direction of the implant is a critical factor in RF-related tissue heating. The actual E-field distribution, which is dependent on phantom/body properties and the MR-system employed, must be considered when assessing the effects of RF power deposition in implant safety investigations., ((c) 2008 Wiley-Liss, Inc.)

We describe the NMR relaxation properties of magnetically labeled cells. The cells are labeled with magnetic nanoparticles (SPIO, USPIO), which generate susceptibility contrast. The geometry of the labeled cells and the surrounding tissue is considered. We assume that the magnetic nanoparticles accumulate to form a magnetic core of radius RC inside the cell. The correlation time tau, which describes the motion of spins around this core, is analyzed. Using the strong collision approach, explicit expressions are derived for the transverse relaxation rate R2* for tissue containing labeled cells as a function of the core radius, the diffusion coefficient, and the concentration of the nanoparticles. The predictions of this model agree well with numerical simulations and experimental data., (Copyright (c) 2005 Wiley-Liss, Inc.)

The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 x 469 mum and a slice thickness of 2 mm. The T(1) imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 +/- 53 mL (100 g . min)(-1) for anesthesia with isoflurane (N = 11) at a mean heart rate (HR) of 455 +/- 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 +/- 40 mL (100 g . min)(-1) (N = 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 +/- 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 +/- 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 +/- 81 mL (100 g . min)(-1) (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 +/- 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N = 4, HR 233 +/- 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research., ((c) 2005 Wiley-Liss, Inc.)

Myocardial fiber structure can be determined with diffusion-weighted (DW) MRI as well as with high-resolution T*(2) imaging. The purpose of the present study was twofold: to provide a more quantitative description of T*(2)-based myocardial fiber contrast, and to compare the T*(2)-based fiber structure with high-resolution (78 microm in-plane, 1-mm slice thickness) DW images of the isolated rat heart at 11.75 T. This study demonstrates that the static dephasing regime is responsible for visualization of myocardial microstructure, and that the dynamic dephasing regime can be neglected. In comparison with DW experiments, T*(2) mapping and DW images yield almost equivalent information on myocardial fiber structure., (Copyright 2003 Wiley-Liss, Inc.)

The investigation of flow behavior in coronary arteries is of great importance for an understanding of heart failure and heart regulation mechanisms. The purpose of the present study was to demonstrate that flow velocity can be quantified in the coronary arteries of the isolated rat heart with high-resolution phase contrast MRI. A phase contrast cine-FLASH imaging sequence was used for flow quantification with an in-plane resolution of 70 microm and a slice thickness of 500 microm. With time-resolved measurements, coronary flow over the heart cycle was analyzed. Furthermore, the flow behavior in coronary stenosis was investigated and the degree of stenosis was quantified with MR phase contrast imaging. To achieve the required spatial resolution and a satisfactory signal-to-noise ratio, the experiments were performed at 11.75 T., (Copyright 2003 Wiley-Liss, Inc.)

The analysis of myocardial microstructure in vivo is important for the determination of myocardial contractility and function. The purpose of the present study was to demonstrate that high-resolution T*2 imaging has the potential to visualize the microstructure of beating, isolated rat hearts. To perform T*2 imaging, a multiple gradient-echo sequence was implemented on an 11.75 Tesla microscopy system. An in-plane resolution of 78 microm and a slice thickness of 250 microm were achieved in 24 min. In comparison to histological sections, the T*2 maps showed an excellent spatial correspondence to the myocardial fiber structure. To demonstrate the utility of this technique, morphologic alterations in myocardial microstructure were investigated in hearts with chronic myocardial infarction. Scar tissue and the extent of the infarcted region were clearly visualized and quantified using high-resolution T*2 imaging., (Copyright 2003 Wiley-Liss, Inc.)

The aim of this pilot study in humans was to investigate the effect of an intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and compared with a theoretical model which allowed determination of the intra- extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9 %). A linear response range of DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow the determination of RBV with intravascular CA., (Copyright 2002 Wiley-Liss, Inc.)

Recently the blood oxygenation level-dependent (BOLD)-related T(2)* of myocardium was derived as an analytical function of intracapillary blood volume, blood oxygenation, and nuclear spin diffusion. The basis of this approach was to approximate the diffusion-induced field fluctuations a nuclear spin is subjected to by strong collision dynamics, i.e., the field fluctuations are uncorrelated. The same analysis is now performed for spin echo experiments that gives myocardial T(2) as a function of the parameters above and the echotime. An analytical relationship between T(2) and T(2)* relaxation is derived. The dependence of T(2) on diffusion, echo time, and blood oxygenation is congruent with simulation and experimental data. Magn Reson Med 42:1004-1010, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Measurement of regional blood volume (RBV) in the myocardium in vivo is important for the assessment of tissue viability and function. The method in this work is based on the acquisition of a T(1) map before and after intravascular contrast agent application. It is known that this method is influenced by perfusion that causes an overestimation of RBV values. In order to solve this problem, the new method is proposed which acquires T(1) maps with slice selective inversion pulses. Due to blood flow nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation time. A model that divides tissue into two compartments is adapted to slice selective inversion in order to derive a simple expression for perfusion-corrected RBV. The aim of the study is to demonstrate the feasibility and accuracy of this technique for quantification of RBV in rat myocardium in vivo. RBV maps were obtained for five rats, and the reproducibility was determined by repeating the experiment several times. A mean RBV value of 12.8 +/- 0.7% (v/v) over all animals was obtained in the myocardium. The results were compared with RBV maps obtained with perfusion-sensitive RBV imaging in the same five rats and with first-pass RBV studies. In order to demonstrate the strength of the new method the vasodilator adenosine was administered and alterations in microcirculation were imaged. Magn Reson Med 42:500-506, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Closed DNA loops containing one or more bent regions are important structures that occur in the regulation of gene expression. We analyze the response of structures of this type to a change in applied rotation (change in linking deficiency, delta Lk). Our results apply to a closed loop formed from an elastic rod that is intrinsically bent in Nb discrete, 20 degrees steps up to a maximum of 240 degrees, the bent regions being initially coplanar with the plane of the relaxed DNA loop. We determine the effect of changing the intrinsic elastic resistance of the DNA loop to bending and torsional deformations. This relative resistance is expressed by Poisson's ratio v, which depends upon the ratio of bending stiffness to torsional rigidity. Poisson's ratio is primarily a function of salt type and concentration. We find that the tertiary structure of DNA loops changes with delta Lk, but that the geometric response can be either of two quite different types, depending upon the precise (Nb, v) pair. For combinations of Nb and v that are above a critical curve (the Fickel curve), the response to increasing delta Lk is nonmonotonic (NMT region): the distance between the loop closure point and its diametric opposite first decreases, then increases, as delta Lk increases. For combinations of Nb and v that are below the Fickel curve (NMT region), the corresponding diameter never increases, but always decreases with increasing delta Lk. In addition to these results, we define and implement a new measure of tertiary structure in closed DNA: the absolute writhe, AWr.

The aim of this pilot-study was to evaluate changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole (DIP) by means of MRI. Twenty healthy volunteers were examined using a multi-echo gradient-echo sequence. The differential myocardial signal response due to the blood oxygen level dependent (BOLD) effect was studied under variable conditions of myocardial oxygen supply caused by the vasodilator DIP. Unlike contrast agents (CA) methods, which require at least two injections of CA and DIP, the presented methods require only a single infusion of DIP. To assess changes in myocardial perfusion, a saturation recovery TurboFLASH (SRTFL) sequence with centric reordering for T1 measurements was used with global and slice-selective spin-preparation (five volunteers). The signal response was measured at baseline conditions and when myocardial blood flow was increased during pharmacological stress with DIP. Administration of DIP induced a 17 +/- 9% increase in T2*. Enhanced perfusion resulted in a 15 +/- 5% decrease of T1 after slice-selective spin preparation and a calculated increase in absolute perfusion of about 5.1 ml/(g x min), which reflects coronary reserve. The study shows that DIP-induced alterations in the relationship between myocardial oxygen supply and demand are detectable in healthy volunteers using T2* and T1 measurements. A combination of T2* and T1 examinations could become a useful diagnostic tool for the non-invasive assessment of myocardial oxygenation and perfusion in patients with coronary artery disease (CAD).

This article presents an analytical approach for the quantification of the blood oxygen level dependent (BOLD) effect in the capillary region. The capillary geometry of myocardium is considered. The relaxation rate R*2 is determined as a function of the capillary radius Rc, the intracapillary volume fraction RBV, and the diffusion coefficient D. When the intracapillary volume fraction is small, the approximation R*2 = RBV x tau(-1) x (square root of (1+(taudeltaomega)2)-1) is valid, with the correlation time tau = (Rc2/4D) x (absolute value (ln RBV)/(1 - RBV)). The predictions of this model agree well with numerical simulations and experimental data of others and with data recently measured by our group.

Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T1 measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T1 sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBVm maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBVm values on blood T1 was found. This is in accordance with a model that has been developed recently relating the dependence of RBVm on T1 of blood to perfusion. For Gd-DTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

Many NMR measurements of cardiac microcirculation (perfusion, intramyocardial blood volume) depend on some kind of assumption of intracapillary-extravascular water exchange rate, e.g., fast exchange. The magnitude of this water exchange rate, however, is still unknown. The intention of this study was to determine a lower limit for this exchange rate by investigating the effect of perfusion on relaxation time. Studies were performed in the isolated perfused cardioplegic rat heart. After slice-selective inversion, the spin lattice relaxation rate of myocardium within the slice was studied as a function of perfusion and compared with a mathematical model which predicts relaxation rate as a function of perfusion and intracapillary-extravascular exchange rate. A linear relationship was found between relaxation rate T(-1) and perfusion P normalized by perfusate/tissue partition coefficient of water, lambda: deltaT(-1) = m x deltaP/lambda with 0.82 < or = m < or = 1.06. Insertion of experimental data in the model revealed that a lower bound of the exchange rate from intra- to extravascular space is 6.6 s(-1) (4.5 s(-1), P < 0.05), i.e., the intracapillary lifetime of a water molecule is less than 150 ms (222 ms, P < 0.05). Based on this finding, the T1 mapping after slice-selective inversion could become a valuable noncontrast NMR method to measure variations of perfusion.

The formation of a topologically closed DNA loop is important in many biological processes, including the regulation of transcription, recombination, and replication. Modeling DNA as an isotropic elastic rod, we use finite element analysis to show that the dependence of the twist (delta Tw) and the writhe (Wr) upon the linking number deficit (delta Lk) is strongly influenced by intrinsic bends. We determine how the geometry of a DNA loop changes as a function of the number of uniformly spaced coplanar 20 degrees bends, oriented so as to open toward the center of the loop. We also calculate the geometry of DNA rods that are smoothly bent to the same extent. The response of both delta Tw and Wr of a bent DNA to changes in delta Lk falls into one of three categories, depending upon the number of bends. For a single bend of 20 degrees, Wr increases monotonically with delta Lk and the change in delta Tw with distance is constant along the entire DNA axis. For two to ten 20 degrees bends, Wr passes first through a local maximum, then through a local minimum, and finally increases monotonically as delta Lk increases. For eleven to eighteen 20 degrees bends, Wr again varies monotonically with delta Lk. For all numbers of bends greater than two, the delta Tw per unit length depends upon the distribution of intrinsic bends, being constant between any two adjoining bends but varying with their position relative to the cut location. Accompanying these delta Lk-associated changes in Wr and delta Tw per unit length are characteristic changes in geometry that are specific for each category. The results of these calculations raise the possibility that intrinsic bends can serve as a control factor in the biological functions associated with loop formation in DNA.

The effect of perfusion on relaxation time in tissue has only been considered for first-pass kinetics of NMR-signal after application of contrast agents. The importance of perfusion on relaxation has not yet been studied for steady state conditions, i.e., when the intravascular relaxation rate is constant in time. The aim of this study is to develop a model in which T1 relaxation is derived as a function of perfusion and intracapillary volume fraction (regional blood volume). Tissue is considered to be two-compartment system, which consists of intracapillary and extravascular space. Intracapillary relaxation differs from relaxation in the arterial system due to diffusion-exchange of magnetization from extravascular to intracapillary space. Perfusion tends to attenuate this difference and thus counteracts the effect on intracapillary relaxation. Relaxation in the extravascular and intracapillary magnetization are linked by diffusion. This dependence is presented in analytical form and a generic equation is derived. AT1 experiment is considered in which all spins of tissue and blood are inverted at the beginning. Calculations are performed for the fast exchange model of tissue. Perfusion increases relaxation enhancement of intravascular contrast agents. This effect is considerable in highly perfused tissue like myocardium. The dependence of relaxation on perfusion implies an overestimation of the regional blood volume when the calculation of the latter is based on tissue models that neglect perfusion. The model presented here is applied to predict the effect of perfusion on T1 imaging with FLASH-pulse sequences because this technique has been proven to be a powerful method to obtain T1 maps within a short time interval. For the fast exchange model, two algorithms are suggested that determine perfusion and regional blood volume from T1 imaging in the presence and absence of intravascular contrast agents.

T1 values of phosphorus metabolites visible in human cardiac 31P-MR spectra were determined in 12 volunteers at 1.5 T. Consecutive spectra were acquired with varying pulse repetition time (TR) from 1.6 to 24 s; volume selection was achieved with ISIS. T1's of creatine phosphate (CP), [gamma-P], [alpha-P], and [beta-P]ATP, 2-3 diphosphoglycerate, and phosphodiesters were 6.1 +/- 0.5, 5.4 +/- 0.5, 5.5 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s, respectively. CP/ATP ratios showed little change with varying TR; linear regression of CP/ATP vs TR was of borderline significance (r = 0.28, P = 0.06). T1's for CP and ATP were also determined in standard solution (20 mM CP, 10 mM ATP) yielding T1CP of 8.7 +/- 0.2 and T1[gamma-P]-ATP of 9.9 +/- 0.7 s. Thus, T1's for CP and ATP were similar at 1.5 T in both human heart and standard solution. In human cardiac 31P-MR spectra, CP/ATP ratios may need little correction for partial saturation.

The role of diffusive transport on the enhancement of nuclear spin relaxation through NMR contrast agents is described by means of diffusion-Bloch equations. These equations are solved in the mean relaxation time approximation [W. Nadler and K. Schulten, J. Chem. Phys. 82, 151-160 (1985)]. A model presented considers relaxation enhancement in tissue in which contrast agents confined to intravascular spaces affect nuclear spin in the extravascular volume. We show how the mean relaxation time depends on capillary density, on permeability, and on diffusion. A second model describes enhanced phase relaxation of liver tissue in the presence of magnetic particles in Kupffer cells. The relationship between relaxation rate and density of Kupffer cells is investigated. The diagnostic value of enhanced nuclear relaxation in the presence of contrast agents is discussed on the basis of the systematic mathematical results obtained.