Simulation of Mb/Hb in NIRS and oxygen gradient in the human and canine skeletal muscles using H-NMR and NIRS.
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Animals↗
Biomedical subjects
John S Leigh
Publications and source records attributed to John S Leigh.
Spatial and temporal characteristics of physiological noise in fMRI at 3T.
RATIONALE AND OBJECTIVES: Physiological noise in blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) has been shown to have characteristics similar to the BOLD signal itself, suggesting that it may have a vascular dependence. In this study, we evaluated the influence of physiological noise in fMRI as revealed by the differences in vasculature sensitivity of gradient-echo echo-planar imaging (GE-EPI) and spin-echo EPI (SE-EPI). MATERIALS AND METHODS: The contribution of physiological noise to the fMRI signal during activation of the visual cortex was assessed by comparing its temporal characteristics with respect to echo time (TE), using both GE-EPI and SE-EPI. The correlation of the noise in fMRI with apparent diffusion coefficient (ADC) and the number of components required to describe its variance, as determined by principal-component analysis (PCA), were also assessed. RESULTS: The SE-EPI data were less affected by a TE-dependence of noise, in contrast to the apparent physiological noise in GE-EPI. Voxel-wise analysis revealed that total apparent noise increased as ADC values increased, and the relationship was different for GE-EPI and SE-EPI. PCA revealed that while the number of components characterizing the noise in SE-EPI data increased in a TE-dependent manner, approaching that of white noise at long echo time, the number of components from GE-EPI data was TE-independent. CONCLUSIONS: The difference in sensitivities to physiological noise between SE-EPI and GE-EPI suggests that extravascular BOLD processes around draining veins contribute significantly to physiological noise in BOLD fMRI, and the suppression of this noise component may enhance SE-EPI BOLD sensitivity at higher fields.
Echo-Planar Imaging↗
Spatial sensitivity and temporal response of spin echo and gradient echo bold contrast at 3 T using peak hemodynamic activation time.
Recent theoretical and experimental work has suggested that spin echo (SE) functional MRI (fMRI) has improved localization of neural activity compared to gradient echo (GE) fMRI at high field strengths, albeit with a decrease in blood oxygenation level-dependent (BOLD) contrast. The present study investigated spatial and temporal variations in GE and SE fMRI at 3 T in response to a brief visual stimulus. The results demonstrate that SE BOLD contrast reaches its maximum amplitude more quickly than does GE contrast at long echo times. We have called this metric the peak hemodynamic activation time (PHAT). Because BOLD changes in response to increased neuronal activity occur earlier in the microvasculature and then later propagate into the venous compartment, these results provide further evidence that SE-based BOLD contrast provides superior localization to the site of activation at 3 T. Spatial overlay of SE and GE PHAT maps onto structural images reveal markedly different spatial profiles and further support the interpretation that shorter peak times correlate to improved spatial sensitivity.
Artifacts↗
Temporal resolving power of spin echo and gradient echo fMRI at 3T with apparent diffusion coefficient compartmentalization.
The temporal resolving power of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T was investigated in the visual and auditory cortices of the human brain. By using controlled temporal delays and selective visual hemifield stimulation, regions with similar (left vs. right occipital cortex) and different (occipital cortex vs. auditory cortex) vascular architectures were compared. Estimates of the time-to-peak (TTP) of the BOLD hemodynamic response function (hrf) were obtained using a spin echo (SE) sequence and compared to those acquired using a traditional gradient echo (GE) sequence. The hrf TTP in the visual cortex was found to be 4.73 s and 4.21 s for GE and SE, respectively. The auditory cortex response was significantly delayed, with TTPs of 4.95 s and 4.51 s for GE and SE, respectively. The GE response was able to resolve visual stimuli separated by 250 ms, whereas SE could resolve stimuli 500 ms apart. Apparent-diffusion-coefficient (ADC) compartmentalization of the BOLD signal was applied to restrict the vascular sensitivity of the SE and GE sequences. Limiting the response to voxels with ADCs < 0.8 x 10(-3) mm(2)/s improved the temporal resolving power of GE and SE BOLD to 125 ms and 250 ms, respectively.
Acoustic Stimulation↗
Indirect detection of lung perfusion using susceptibility-based hyperpolarized gas imaging.
PURPOSE: To address the problem of inadequate signal-to-noise ratio (SNR) encountered in lung perfusion magnetic resonance imaging (MRI) by developing an indirect detection based on the strong hyperpolarized (HP) gas signal. MATERIALS AND METHODS: Our model is based on detecting the effects of gadolinium (Gd) flowing through lung capillaries by recording the phase of the nearby alveolar HP gas. In a HP gas 3He phantom we imaged gas phases before and after removing tubes containing paramagnetic solution away from the phantom. We also imaged HP gas phases in pig lungs before and after injection of Gd. Finally, parenchymal spin phase in excised lungs was measured as a function of Gd concentration. RESULTS: In the phantom, the differential phase map displayed a pattern characteristic of a susceptibility-induced dipole field, showing the possibility of an indirect detection. In vivo, the differential phase map showed homogeneous appearance, as expected for uniform perfusion in healthy lungs. Ex vivo, the parenchymal spin phases were shown to depend linearly on Gd concentration. CONCLUSION: Our method should allow indirect perfusion (Q) and direct ventilation (V) to be assessed simultaneously, thus allowing for diagnosis of V/Q mismatches. The linear dependency of parenchymal spin phase vs. Gd concentration may allow for quantification of lung perfusion.
Animals↗
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.
Algorithms↗
Quantifying arbitrary magnetic susceptibility distributions with MR.
Magnetic susceptibility, as a physical property of materials, plays important roles in many physical, chemical, engineering, and medical applications. Its quantification becomes of significant interest when MRI becomes a commonly used technique in biomedical applications. A general method is presented here for quantifying arbitrary magnetic susceptibility distributions in a localized region on the basis of first principles of magnetic induction field distributions in space. A proof of the concept was demonstrated by computer simulations. The study establishes the methodological basis for quantitative magnetic susceptibility imaging with MR.
Computer Simulation↗
Proton MRI of metabolically produced H2 17O using an efficient 17O2 delivery system.
In vivo detection of H(2)(17)O produced via metabolic reduction of inhaled (17)O-enriched gas is demonstrated using proton magnetic resonance imaging (MRI). Specifically, (1)H T(1rho)-weighted MRI, which may be readily implemented on any MRI scanner, is applied as an indirect (17)O imaging method to quantitatively monitor the distribution of metabolically produced (17)O water (mpH(2)(17)O) in the rat brain. The delivery of (17)O(2) to rats is conducted via a specially designed closed respiration circuit that conserves the expensive gas. Quantitative mapping of H(2)(17)O performed via (1)H T(1rho)-weighted MRI is validated by direct (17)O-magnetic resonance spectroscopy. The MRI data show that a steady-state H(2)(17)O concentration of 25.7 +/- 1.66 mM (n = 4) is achieved in the rat brain within approximately 30 min under the (17)O inhalation paradigm used. From the first minute of the mpH(2)(17)O time courses, cerebral metabolic rate of oxygen (CMRO(2)) is estimated to be 2.10 +/- 0.44 micromol g(-1) min(-1) (n = 4), a value that is consistent with the literature.
Animals↗
Muscle metabolism with blood flow restriction in chronic fatigue syndrome.
The purpose of this study was to determine whether chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to Centers for Disease Control criteria (n = 19) were compared with normal sedentary subjects (n = 11). Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle with (31)P-magnetic resonance spectroscopy. Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients. Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow. In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery but no evidence that this impaired muscle metabolism. Thus CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms.
Adult↗
High-resolution assessment of blood flow in murine RIF-1 tumors by monitoring uptake of H(2)(17)O with proton T(1rho)-weighted imaging.
Perfusion parameters, such as blood flow, are critical properties of tumors related to angiogenesis, drug delivery, radiosensitivity, bioenergetic status, and steady state levels of metabolites, such as lactate, that have been proposed as indices of tumor response to therapy. The existing MR methods for measuring tumor blood flow (TBF) have limitations related to sensitivity, spatial resolution, or dependence on other physiological properties such as vascular permeability. To address many of these difficulties, this study introduces the use of an (17)O-enriched tracer in conjunction with high-resolution, indirect MRI to measure TBF. To demonstrate the advantages of this technique, relative TBF was measured in subcutaneous RIF-1 tumors in C3H mice by monitoring the uptake of H(2) (17)O with a resolution of 0.16 x 0.31 x 3 mm in 13 sec. At this resolution, tumor heterogeneity with respect to blood flow is clearly visible. Measurement of the tracer arterial input function, which is necessary for determination of absolute blood flow, may be facilitated with improved temporal resolution.
Animals↗
Indirect 17(O)-magnetic resonance imaging of cerebral blood flow in the rat.
Proton T(1rho)-dispersion MRI is demonstrated for indirect, in vivo detection of (17)O in the brain. This technique, which may be readily implemented on any clinical MRI scanner, is applied towards high-resolution, quantitative mapping of cerebral blood flow (CBF) in the rat by monitoring the clearance of (17)O-enriched water. Strategies are derived and employed for 1) quantitation of absolute H(2) (17)O tracer concentration from a ratio of high- and low-frequency spin-locked T(1rho) images, and 2) mapping CBF without having to transform the T(1rho) signal to H(2) (17)O tracer concentration. Absolute regional blood flow was mapped in a single 3-mm brain slice at an in-plane resolution of 0.4 x 0.8 mm within a 5-min tracer washout time; these data are consistent with the less localized CBF measurements reported in the literature. T(1rho)-weighted imaging yields excellent signal-to-noise ratios, spatiotemporal resolution, and anatomical contrast for mapping CBF.
Animals↗
Probing rat brain oxygenation with near-infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI).
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Animals↗
T1rho MR imaging of the human wrist in vivo.
RATIONALE AND OBJECTIVES: The purpose of this study was (a) to demonstrate the feasibility of computing T1rho maps of, and T1rho dispersion in, human wrist cartilage at MR imaging in vivo and (b) to compare T1rho and T2 weighting in terms of magnitude of relaxation times and signal intensity contrast. MATERIALS AND METHODS: T2 and T1rho magnetic resonance images of wrist joints in healthy volunteers (n = 5) were obtained with a spin-echo sequence and a fast spin-echo sequence pre-encoded with a spin-lock pulse cluster. A 1.5-T clinical imager was used (Signa; GE Medical Systems, Milwaukee, Wis) with a 9.5-cm-diameter transmit-receive quadrature birdcage coil tuned to 63.75 MHz. RESULTS: T1rho relaxation times at a spin-lock frequency of 500 Hz vary from 40.5 msec +/- 0.85 to 56.6 msec +/- 4.83, and T2 relaxation times vary from 28.1 msec +/- 1.88 to 34.5 msec +/- 2.63 (mean +/- standard error of the mean, n = 5, P < .016) in various regions of the wrist. T1rho dispersion was observed in the range of spin-lock frequencies studied. T1rho-weighted images not only have higher signal-to-noise ratios but also show better fluid and fat signal suppression than T2-weighted images. CONCLUSION: It was possible to perform T2- and T1rho-weighted MR imaging of human wrist cartilage in vivo with standard clinical imagers. The higher signal-to-noise ratio and improved contrast between cartilage and surrounding fat achieved with T1rho imaging may provide better definition of lesions and accurate quantitation of small changes in cartilage degeneration.
Adult↗
Artifacts in T(1rho)-weighted imaging: correction with a self-compensating spin-locking pulse.
Significant artifacts arise in T(1rho)-weighted imaging when nutation angles suffer small deviations from their expected values. These artifacts vary with spin-locking time and amplitude, severely limiting attempts to perform quantitative imaging or measurement of T(1rho) relaxation times. A theoretical model explaining the origin of these artifacts is presented in the context of a T(1rho)-prepared fast spin-echo imaging sequence. Experimentally obtained artifacts are compared to those predicted by theory and related to B(1) inhomogeneity. Finally, a "self-compensating" spin-locking preparatory pulse cluster is presented, in which the second half of the spin-locking pulse is phase-shifted by 180 degrees. Use of this pulse sequence maintains relatively uniform signal intensity despite large variations in flip angle, greatly reducing artifacts in T(1rho)-weighted imaging.
Artifacts↗
Blood flow and muscle metabolism in chronic fatigue syndrome.
The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and oxidative delivery to skeletal muscle. Patients with CFS according to CDC (Center for Disease Control) criteria ( n =19) were compared with normal sedentary subjects ( n =11). Muscle blood flow was measured with Doppler ultrasound after cuff ischaemia and exercise. Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemic oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous wavelength near-IR spectroscopy. Muscle metabolism was measured using (31)P magnetic resonance spectroscopy. CFS patients and controls were not different in the peak blood flow after cuff ischaemia, the rate of recovery of phosphocreatine after submaximal exercise, and the rate of recovery of oxygen saturation after cuff ischaemia. In conclusion, CFS patients showed no deficit in blood flow or oxidative metabolism. This suggests that CFS symptoms do not require abnormal peripheral function.
Adult↗
Fast MRI of RF heating via phase difference mapping.
A method is presented for the rapid acquisition of temperature maps derived from phase difference maps. The temperature-dependent chemical shift coefficients (TDCSCs) of various concentrations of aqueous cobalt and dysprosium-based compounds were measured. The largest TDCSC calculated was for 100 mM DyEDTA, which had a TDCSC of -0.09 PPM/K; 160 mM CoCl2 had a TDCSC of -0.04 PPM/K. These temperature-dependent chemical shifts (TDCSs) result in phase changes in the MR signal with changing temperature. Agarose phantoms were constructed with each paramagnetic metal. A fast gradient-echo (FGRE) MR image was acquired to serve as the baseline image. A "test" MRI procedure was then performed on the phantom. Immediately afterwards, a second FGRE MR image was acquired, serving as the probing image. Proper image processing as a phase difference map between the probing image and the baseline image resulted in an image which quantitatively described the temperature increase of the phantom in response to a particular "test" imaging experiment. Applications of this technique in assessing the safety of pulse sequences and MR coils are discussed.
Biophysical Phenomena↗
Pulmonary ventilation and perfusion scanning using hyperpolarized helium-3 MRI and arterial spin tagging in healthy normal subjects and in pulmonary embolism and orthotopic lung transplant patients.
Conventional nuclear ventilation/perfusion (V/Q) scanning is limited in spatial resolution and requires exposure to radioactivity. The acquisition of pulmonary V/Q images using MRI overcomes these difficulties. When inhaled, hyperpolarized helium-3 ((3)He) permits MRI of gas distribution. Magnetic labeling of blood (arterial spin-tagging (AST)) provides images of pulmonary perfusion. Three normal subjects, two patients who had undergone single lung transplantation for emphysema, and one subject with pulmonary embolism (PE), were imaged. (3)He distribution and blood perfusion appeared uniform in the normal subjects and throughout the lung allografts. Gas distribution and perfusion in the emphysematous lungs were non-uniform and paralleled radiographic abnormalities. AST imaging alone revealed a lower-lobe wedge-shaped perfusion defect in the patient with PE that corresponded to computed tomography (CT) imaging. Hyperpolarized (3)He gas is demonstrated to provide ventilation images of the lung. Blood perfusion information may be obtained during the same examination using the AST technique. The sequential application of these imaging methods provides a novel tool for studying V/Q relationships.
Helium↗
Chemical-shift MR imaging of acetic acid during percutaneous chemical ablation therapy: preliminary work.
The purpose of this study was to test the hypothesis that chemical-shift magnetic resonance (MR) imaging may be used to map the distribution of acetic acid during percutaneous chemical ablation procedures. Chemical-shift MR imaging was performed with use of standard methods on a 1.5-T scanner. Phantom and ex-vivo data demonstrated focal increases in the observed signal in chemical-shift MR imaging that correlate well with the site of injection. Preliminary study in a patient with hepatoma revealed focal signal at the injection site. These preliminary results suggest that chemical-shift MR imaging may be used to visualize acetic acid distribution during percutaneous chemical ablation procedures.
Acetic Acid↗