Oxygen-sensitive contrast in blood for steady-state free precession imaging.

Steady-state free precession (SSFP) methods have gained widespread recognition for their ability to provide fast scans at high signal-to-noise ratio. This paper demonstrates that such methods are also capable of reflecting functional information, particularly blood oxygenation state. It is well known that SSFP signals show substantial sensitivity to small off-resonance frequency variations. However, that mechanism cannot explain the oxygen-sensitive contrast in blood that was observed with steady-state methods using phase-cycled radiofrequency pulses. From theoretical and experimental models it is demonstrated that the mechanism responsible for such contrast originates from the motion of spins through local field inhomogeneities in and around deoxygenated red blood cells. In addition, this work shows that it is critical to choose the scan parameters carefully for robust oxygen-sensitive contrast. Finally, it is demonstrated that it is possible to build a quantitative model that incorporates the Luz-Meiboom model, which had been used in the past to estimate quantitative measures of vascular blood oxygen levels. It is envisioned that this method could be instrumental in real-time imaging focused on detecting diseases where the oxygen state of blood is impaired.     

Spoiling of transverse magnetization in steady-state sequences.

A detailed analysis is presented of a method to eliminate transverse magnetization prior to each rf excitation in pulse sequences with TR less than T2. It is shown that artifact-free images with high T1 contrast can be obtained only if a phase shift that is incremented during each TR interval is applied to the transverse magnetization. Computer simulations are used to show that when this phase increment is 117 degrees, the steady-state transverse magnetization prior to each rf pulse is nulled over a wide range of T1, T2, and rf tip angles, resulting in optimal T1 contrast. Such nulling of steady-state transverse magnetization cannot be obtained by using large gradient pulses, or gradients of random or linearly incremented amplitude. Images of phantoms and human subjects confirm the theoretical predictions.     

Physiologic alterations in cranial blood flow demonstrated by magnetic resonance angiography.

Two-dimensional phase contrast magnetic resonance angiography (MRA) was used to image alterations in cranial blood flow induced by changes in arterial PCO2 in an animal model. MRA was performed on five sheep; 64 acquisitions were obtained in each of three flow encode directions using a 256 x 256 matrix. Sheep were intubated and ventilated with oxygen and 1.5% halothane to prevent any movement. Femoral arterial cannulation was performed to monitor arterial blood gases and pressure. The sheep was secured in a cradle with its head and neck in a 6-inch imaging coil within the 26-cm-clear bore. Images were obtained during separate physiologic states, which were induced by changes in ventilatory parameters. These were normocapnia (PCO2 35-45 mm Hg), hypercapnia (greater than 90-130 mm Hg), and hypercapnia with superimposed hypoxia. Comparisons of images were performed using both a video flashback mode and image subtraction. The authors noted that 1) both venous and arterial flow velocity qualitatively increased during hypercapnia; 2) in addition to change in the caliber of blood vessels, redistribution of blood flow within the cranium could be demonstrated during the PCO2 changes; and 3) blood was directed away from superficial structures and toward the brain during superimposed hypoxia. MRA, previously used to show steady-state cranial flow also can demonstrate flow responses to physiologic stimuli.     

High-resolution MRI of cardiac function with projection reconstruction and steady-state free precession.

The purpose of this study was to investigate the trabecular structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 x 0.8 x 8 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall.     

Influence of body temperature on the BOLD effect in murine SCC tumors.

Changes in the blood oxygen level dependent (BOLD) enhancements in tumors (squamous cell carcinoma, (SCCVII)) implanted in mice maintained at core temperatures of 30 degrees C or 37 degrees C were measured using MRI and compared to tumor oxygen levels obtained using an oxygen-sensitive Eppendorf electrode. Tumors were implanted in a hindleg of the mice intramuscularly. Tumor-bearing mice were imaged by BOLD MRI, while first breathing air and then carbogen (95% O2, 5% CO2) for 15-min intervals at a core temperature of 30 degrees C. After an equilibration period, the identical regimen was conducted with the same animal maintained at 37 degrees C. This procedure was repeated with additional mice starting at 37 degrees C followed by imaging at 30 degrees C. Likewise, oxygen electrode measurements of the tumor were determined at core temperatures of 30 degrees C and 37 degrees C. The Eppendorf measurements showed that tumors in animals maintained at 30 degrees C were significantly more hypoxic than at 37 degrees C. MRI studies demonstrated stronger BOLD enhancement at 30 degrees C than at 37 degrees C, suggesting significant changes in hypoxia and/or blood flow in tumors at these temperatures. The findings of the study stress the importance of maintaining normal core temperature when assessing tumor oxygen status using functional imaging modalities or oxygen-sensitive electrodes.     

Influence of intravascular activity on the determination of blood flow and oxygen extraction in normal and ulcerated legs using the 15O steady-state technique and positron emission tomography

An analysis using the 15O steady-state inhalation technique has been carried out into the effects of correction for intravascular activity on the determination of blood flow and oxygen extraction ratio (OER) in the legs of patients affected by ulceration. Transaxial images of the distribution of activity in a plane passing through the ulcer were obtained during steady-state inhalation of C15O2 and 15O2, respectively, using a single slice positron emission tomographic scanner. From these, the basic tracer model equations were solved to obtain blood flow and oxygen extraction with and without additional correction for the presence of intravascular activity. The latter was obtained from a scan following the inhalation of a tracer quantity of 11CO, which labels the red blood cell pool. Mean blood flow and OER in ulcerated regions were 0.087 ml/ml/min and 0.33, respectively. With correction for blood volume, assumed to be all venous, the mean OER decreased to 0.12. In the "mirror" region of normal legs mean blood flow was 0.011 ml/ml/min with uncorrected and corrected OER values of 0.87 and 0.75, respectively. The effect of assuming a nonzero arterial volume increases as flow and OER decrease but is uncertain due to the unknown arterial fraction. Correction for intravascular 15O is essential and generally the assumption that all blood volume is venous is adequate.     

Monitoring blood oxygen state in muscle microcirculation with transverse relaxation.

Oxygen uptake from the microcirculation is a direct measure of tissue function. Magnetic resonance is capable of detecting differences between oxygenated and deoxygenated blood due to the paramagnetic properties of deoxyhemoglobin. At the level of the microcirculation, however, imaging methods cannot directly visualize the vessels. Instead, bulk MR parameters are investigated for their ability to monitor blood oxygen saturation (%O(2)) changes in the microcirculation of tissue, specifically skeletal muscle. Experiments in an in vitro model verified the feasibility of detecting changes in exponential decay signals, and also verified the prediction of only two distinct decay components. Experiments in a rabbit model demonstrate that T(2)' and monoexponential T(2) decay are not sensitive to blood oxygen changes, but that the long-T(2) component in a biexponential fit is correlated to the blood oxygen state. Assuming a two-pool model for water protons in muscle, and with knowledge of the T(2)-%O(2) relation, estimates of the microcirculation blood oxygen state can be made with some reasonable assumptions. Magn Reson Med 45:662-672, 2001.     

Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging

Intravoxel incoherent motion (IVIM) imaging is a method the authors developed to visualize microscopic motions of water. In biologic tissues, these motions include molecular diffusion and microcirculation of blood in the capillary network. IVIM images are quantified by an apparent diffusion coefficient (ADC), which integrates the effects of both diffusion and perfusion. The aim of this work was to demonstrate how much perfusion contributes to the ADC and to present a method for obtaining separate images of diffusion and perfusion. Images were obtained at 0.5 T with high-resolution multisection sequences and without the use of contrast material. Results in a phantom made of resin microspheres demonstrated the ability of the method to separately evaluate diffusion and perfusion. The method was then applied in patients with brain and bone tumors and brain ischemia. Clinical results showed significant promise of the method for tissue characterization by perfusion patterns and for functional studies in the evaluation of the microcirculation in physiologic and pathologic conditions, as, for instance, in brain ischemia.     

Mr perfusion studies with t1-weighted echo planar imaging

The T₁ perfusion model has worked well in brain functional studies where flow changes are measured. Using selective and nonselective inversion pulses, a new method has been developed to study steady-state brain blood flow. The authors obtained flow-sensitive images using selective inversion and flow-insensitive images using nonselective inversion. Subtraction of flow-insensitive images from flow-sensitive images gave us flow-weighted images with good gray-white flow contrast in cortical gray matter as well as in the thalamus and basal ganglia. Fitting T₁S of flow-insensitive and flow-sensitive images allowed us to obtain preliminary results of brain blood flow maps. Two specific problems can seriously affect the accuracy of the brain blood flow values and the gray-white flow contrast of brain blood flow maps. These are the problems of the partial volume effect of CSF and gray matter, and the difference between blood T₁ and white matter T₁. The authors discuss in detail the character of these problems and present a number of approaches to manage such problems.     

Measuring random microscopic motion of water in tissues with MR imaging: a cat brain study

Cat brain images sensitized to incoherent motion by additional gradient pulses were obtained on a 4.7 T magnetic resonance unit equipped with shielded gradient coils. The apparent diffusion coefficient of water in gray and white matter was accurately determined and imaged from the signal attenuation curve obtained as a function of gradient strength. Contrast in calculated diffusion images differed from typical T2-weighted contrast. Furthermore, in gray matter and in areas containing flowing CSF the attenuation curve was found to be biexponential. These results are interpreted in terms of a simple voxel model with microcirculation and diffusion contributions.     

NMR imaging in the diagnosis and management of intracranial angiomas

Fourteen intracranial angiomas were clearly visualized and diagnosed with certainty on fast saturation-recovery images, which highlight blood vessels without the use of contrast media, and on steady-state free-precession images, in which the moving blood leads to removal of signal. Performed as the initial investigation, nuclear magnetic resonance obviates angiography when the site and extent of the angioma would preclude operation, and in other cases provides useful anatomic information complementing the angiogram. When clinical presentation follows hemorrhage the size and position of the associated hematoma can be reliably assessed.     

T1rho contrast in functional magnetic resonance imaging.

The application of T1 in the rotating frame (T1rho) to functional MRI in humans was studied at 3 T. Increases in neural activity increased parenchymal T1rho. Modeling suggested that cerebral blood volume mediated this increase. A pulse sequence named spin-locked echo planar imaging (SLEPI) that produces both T1rho and T2* contrast was developed and used in a visual functional MRI (fMRI)experiment. Spin-locked contrast significantly augments the T2* blood oxygen level-dependent (BOLD) contrast in this sequence. The total functional contrast generated by the SLEPI sequence (1.31%) was 54% larger than the contrast (0.85%) obtained from a conventional gradient-echo EPI sequence using echo times of 30 ms. Analysis of image SNR revealed that the spin-locked preparation period of the sequence produced negligible signal loss from static dephasing effects. The SLEPI sequence appears to be an attractive alternative to conventional BOLD fMRI, particularly when long echo times are undesirable, such as when studying prefrontal cortex or ventral regions, where static susceptibility gradients often degrade T2*-weighted images.     

Assessment of tumor blood perfusion by high-resolution dynamic contrast-enhanced MRI: a preclinical study of human melanoma xenografts.

A noninvasive method to obtain high-resolution images of tumor blood perfusion is needed for individualized cancer treatments. In this study we investigated the potential usefulness of dynamic contrast-enhanced MRI (DCE-MRI), using human melanoma xenografts as models of human cancer. Gadopentetate dimeglumine (Gd-DTPA) was used as the contrast agent, and DCE-MRI was performed at a voxel size of 0.5 x 0.2 x 2.0 mm3 with spoiled gradient-recalled sequences. We obtained images of E. F (where E is the extraction fraction, and F is perfusion) by subjecting DCE-MR images to Kety analysis. We obtained highly reproducible E. F images, which we verified by imaging heterogeneous tumors twice. We hypothesized that the extraction fraction of Gd-DTPA would be high and would not vary significantly in tumor tissue, implying that E. F should be a well-suited parameter for describing tumor blood perfusion. Observations consistent with this hypothesis were made by comparison of E. F-images with immunostained histological preparations from the imaged sections. The E. F images mirrored the histological appearance of the tumor tissue perfectly. Quantitative studies showed that E. F was highest in nonhypoxic tissue with high microvascular density, second highest in nonhypoxic tissue with low microvascular density, third highest in hypoxic tissue, and lowest in necrotic tissue. Moreover, the radial heterogeneity in E. F was almost identical to that in the blood supply, as assessed by the use of Na99mTcO4 as a perfusion tracer. Taken together, our observations show that high-resolution images reflecting tumor blood perfusion can be obtained by DCE-MRI.     

Simultaneous noninvasive determination of regional myocardial perfusion and oxygen content in rabbits: toward direct measurement of myocardial oxygen consumption at MR imaging.

PURPOSE: To determine whether myocardial arterial perfusion and oxygen concentration can be quantified simultaneously from the same images by using spin labeling and the blood oxygenation level-dependent (BOLD) effect with fast spin-echo (SE) imaging. MATERIALS AND METHODS: A T2-weighted fast SE pulse sequence was written to image isolated, arrested, blood-perfused rabbit hearts (n = 6) at 4.7 T. Perfusion images with intensity in units of milliliters per minute per gram that covered the entire left ventricle with 0.39 x 0.39 x 3.00-mm resolution were obtained in less than 15 minutes with a 32-fold reduction in imaging time from that of a previous study. Estimates of oxygen concentration were made from the same images acquired for calculation of perfusion images. RESULTS: Estimates of regional myocardial oxygen content could be made from the perfusion images; this demonstrated the feasibility of three-dimensional calculation of regional oxygen consumption, which requires concomitant measurement of both oxygen content and flow. Fast SE imaging was shown to be as sensitive to hemoglobin desaturation as standard SE imaging. Perfusion abnormalities and oxygen deficits were easily identified and verified qualitatively with gadopentetate dimeglumine on both perfusion and BOLD images obtained after coronary arterial ligation. CONCLUSION: T2-weighted fast SE imaging combined with perfusion-sensitive spin labeling can be used to measure myocardial arterial perfusion and oxygen concentration. This provides the groundwork for calculation of regional myocardial oxygen consumption.     

Rapid fat-suppressed isotropic steady-state free precession imaging using true 3D multiple-half-echo projection reconstruction.

Three-dimensional projection reconstruction (3D PR)-based techniques are advantageous for steady-state free precession (SSFP) imaging for several reasons, including the capability to achieve short repetition times (TRs). In this paper, a multi-half-echo technique is presented that dramatically improves the data-sampling efficiency of 3D PR sequences while it retains this short-TR capability. The k-space trajectory deviations are measured quickly and corrected on a per-sample point basis. A two-pass RF cycling technique is then applied to the dual-half-echo implementation to generate fat/water-separated images. The resultant improvement in the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was demonstrated in volunteer studies. Volumetric images with excellent spatial resolution, coverage, and contrast were obtained with high speed. The non-contrast-enhanced SSFP studies show that this technique has promising potential for MR angiography (MRA).     

A new steady-state imaging sequence for simultaneous acquisition of two MR images with clearly different contrasts

We present a new steady-state imaging sequence, which simultaneously allows in a single acquisition the formation of two MR images with clearly different contrasts. The contrast of the first image is FISP-like, whereas the second image is strongly T2-weighted. In principle the T2 values in the image can be calculated from the combination of the first and second images. We also show calculated T2 images.     

The central signal singularity phenomenon in balanced SSFP and its application to positive-contrast imaging

Small perturbations of steady-state sequence parameters can induce very large spectral profile deviations that are localized to specific off-resonant frequencies, denoted critical frequencies. Although, a small number of studies have previously considered the use of these highly specific modulations for MR angiography and elastography, many potential applications still remain to be explored. An analysis of this phenomenon using a linear systems technique and a geometric magnetization trajectory technique shows that the critical frequencies correspond to singularities in the steady-state signal equation. An interleaved acquisition combined with a complex difference technique yields a spectral profile containing sharp peaks interleaved with wide stopbands, while a complex sum technique yields a spectral profile similar to that of balanced steady-state free precession. Simulations and phantom experiments are used to demonstrate a novel application of this technique for positive-contrast imaging of superparamagnetic iron-oxide nanoparticles. The technique is shown to yield images with high levels of positive contrast and good water and fat background suppression. The technique can also simultaneously yield images with contrast similar to balanced steady-state free precession.     

Fast phase-contrast velocity measurement in the steady state.

A new method of encoding flow velocity as image phase in a refocused steady-state free precession (SSFP) sequence, called steady-state phase contrast (SSPC), can be used to generate velocity images rapidly while retaining high signal. Magnitude images with refocused-SSFP contrast are simultaneously acquired. This technique is compared with the standard method of RF-spoiled phase contrast (PC), and is found to have more than double the phase-signal to phase-noise ratio (PNR) when compared with standard PC at reasonable repetition intervals (TRs). As TR decreases, this advantage increases exponentially, facilitating rapid scans with high PNR efficiency. Rapid switching between the two necessary steady states can be accomplished by the insertion of a single TR interval with no flow-encoding gradient. The technique is implemented in a 2DFT sequence and validated in a phantom study. Preliminary results indicate that further TR reduction may be necessary for high-quality cardiac images; however, images in more stationary structures, such as the descending aorta and carotid bifurcation, exhibit good signal-to-noise ratio (SNR) and PNR. Comparisons with standard-PC images verify the PNR advantage predicted by theory.     

Myocardial perfusion and intracapillary blood volume in rats at rest and with coronary dilatation: MR imaging in vivo with use of a spin-labeling technique

PURPOSE: To validate a magnetic resonance (MR) imaging technique that is not first pass and that reveals perfusion and regional blood volume (RBV) in the intact rat. MATERIALS AND METHODS: Measurement of perfusion was based on the perfusion-sensitive T1 relaxation after magnetic spin labeling of water protons. RBV was determined from steady-state measurements of T1 before and after administration of an intravascular contrast agent. The colored microsphere technique was used as a reference method for perfusion measurement. RBV and perfusion maps were obtained with the rats at rest and during administration of 3 mg of adenosine phosphate per kilogram of body weight per minute. RESULTS: At MR imaging, perfusion during resting conditions was 3.5 mL/g/min +/- 0.1 (SEM), and RBV was 11.6% +/- 0.6 (SEM). Adenosine phosphate significantly increased perfusion to 4.5 mL/g/min +/- 0.3 (SEM) and decreased mean arterial pressure from 120 mm Hg to 65 mm Hg, which implies a reduction of coronary resistance to 40% of baseline. RBV increased consistently to 23.8% +/- 0.6 (SEM). CONCLUSION: The study results show that quantitative mapping of perfusion and RBV may be performed noninvasively by means of MR imaging in the intact animal. The presented method allows determination of vasodilative and perfusion reserve, which reflects the in vivo regulation of coronary microcirculation for a given stimulus.     

Three-dimensional steady-state MR angiography of the lower extremities

Volume steady-state black-blood magnetic resonance imaging was evaluated as a method for depicting lower extremity vasculature. In steady-state imaging, flow has low signal intensity because motion destroys the coherence of transverse magnetization. To optimize image contrast, computations and measurements were obtained for the three-dimensional (3D) GRASS (gradient-recalled acquisition in the steady state) and 3D SSFP (steady-state free precession) sequences and a range of TRs and flip angles to determine optimal vessel-muscle contrast. The best results were achieved with a 3D GRASS sequence with a TR msec/TE msec of 25/5 and a flip angle of 30°. Coronal images of the femoral and popliteal vessels were obtained in healthy volunteers with various fields of view and voxel sizes. Inflow of unsaturated spins from outside the image region, yielding high signal intensity, could be a potential drawback in steady-state black-blood imaging; however, problems can be avoided by using coronal acquisitions and large fields of view. Steady-state black-blood imaging depicts vessels with high accuracy and is faster and free of flow artifacts.