Biomedical subjects

Mark S Conradi

Publications and source records attributed to Mark S Conradi.

17 recordsLinked to original sources

PubMed2006

How accurately can the parameters from a model of anisotropic 3He gas diffusion in lung acinar airways be estimated? Bayesian view.

In the framework of a recently proposed method for in vivo lung morphometry, acinar lung airways are considered as a set of randomly oriented cylinders covered by alveolar sleeves. Diffusion of (3)He in each airway is anisotropic and can be described by distinct longitudinal and transverse diffusion coefficients. This macroscopically isotropic but microscopically anisotropic model allows estimation of these diffusion coefficients from multi b-value MR experiments despite the airways being too small to be resolved by direct imaging. Herein a Bayesian approach is used for analyzing the uncertainties in the model parameter estimates. The approach allows evaluation of relative errors of the parameter estimates as functions of the "true" values of the parameters, the signal-to-noise ratio, the maximum b-value and the total number of b-values used in the experiment. For a given set of the "true" diffusion parameters, the uncertainty in the estimated diffusion coefficients has a minimum as a function of maximum b-value and total number of data points. Choosing the MR pulse sequence parameters corresponding to this minimum optimizes the diffusion MR experiment and gives the best possible estimates of the diffusion coefficients. The mathematical approach presented can be generalized for models containing arbitrary numbers of estimated parameters.

Anisotropy↗

PubMed2006

In vivo lung morphometry with hyperpolarized 3He diffusion MRI in canines with induced emphysema: disease progression and comparison with computed tomography.

Despite a long history of development, diagnostic tools for in vivo regional assessment of lungs in patients with pulmonary emphysema are not yet readily available. Recently, a new imaging technique, in vivo lung morphometry, was introduced by our group. This technique is based on MRI measurements of diffusion of hyperpolarized (3)He gas in lung air spaces and provides quantitative in vivo tomographic information on lung microstructure at the level of the acinar airways. Compared with standard diffusivity measurements that strongly depend on pulse sequence parameters (mainly diffusion time), our approach evaluates a "hard number," the average acinar airway radius. For healthy dogs, we find here a mean acinar airway radius of approximately 0.3 mm compared with 0.36 mm in healthy humans. The purpose of the present study is the application of this technique for quantification of emphysema progression in dogs with experimentally induced disease. The diffusivity measurements and resulting acinar airway geometrical characteristics were correlated with the local lung density and local lung-specific air volume calculated from quantitative computed tomography data obtained on the same dogs. The results establish an important association between the two modalities. The observed sensitivity of our method to emphysema progression suggests that this technique has potential for the diagnosis of emphysema and tracking of disease progression or improvement via a pharmaceutical intervention.

Animals↗

PubMed2006

Relaxation and diffusion of perfluorocarbon gas mixtures with oxygen for lung MRI.

We report measurements of free diffusivity D(0) and relaxation times T(1) and T(2) for pure C(2)F(6) and C(3)F(8) and their mixtures with oxygen. A simplified relaxation theory is presented and used to fit the data. The results enable spatially localized relaxation time measurements to determine the local gas concentration in lung MR images, so the free diffusivity D(0) is then known. Comparison of the measured diffusion to D(0) will express the extent of diffusion restriction and allow the local surface-to-volume ratio to be found.

Data Interpretation, Statistical↗

PubMed2006

Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema.

Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.

Administration, Inhalation↗

PubMed2005

Long-range diffusion of hyperpolarized 3He in explanted normal and emphysematous human lungs via magnetization tagging.

Long-range diffusivity of hyperpolarized 3He gas was measured from the decay rate of sinusoidally modulated longitudinal nuclear magnetization in three normal donor and nine severely emphysematous explanted human lungs. This (long-range) diffusivity, which we call Dsec, is measured over seconds and centimeters and is approximately 10 times smaller in healthy lungs (0.022 cm2/s) than the more traditionally measured Dmsec, which is measured over milliseconds and submillimeters. The increased restriction of Dsec reflects the complex, tortuous paths required to navigate long distances through the maze of branching peripheral airways. In emphysematous lungs, Dsec is substantially increased, with some regions showing nearly the unrestricted value of the self-diffusion coefficient (0.88 cm2/s for dilute 3He in air, a 40-fold increase). This suggests the presence of large collateral pathways opened by alveolar destruction that bypass the airways proper. This destruction was confirmed by comparison with histology in seven lungs and by removal of trapped gas via holes in the pleural surface in five lungs.

Emphysema↗

PubMed2005

19F MR imaging of ventilation and diffusion in excised lungs.

Perfluorinated gases, particularly C2F6, are potentially suitable alternatives to hyperpolarized noble gases for pulmonary airspace spin density and diffusion MRI. This work focuses mainly on 19F imaging of C2F6 gas in healthy and emphysematous explanted lungs, avoiding regulatory issues of human in vivo measurements. Three-dimensional gradient echo and spin echo spin density images of human lungs can be made in 10 s with adequate signal-to-noise, demonstrating the feasibility for breathing dynamics to be captured during a succession of short breath holds. As expected, the spin echo images have much smaller susceptibility artifacts than the gradient echo images. 19F and 3He images of the same lungs are compared. The apparent diffusion coefficient (ADC) of C2F6 is sensitive to restrictions imposed by the lung microstructure: the average ADC is measured to be 0.018 cm2/s in healthy lungs versus 0.031 cm2/s in emphysematous lungs at a diffusion time Delta=2.2 ms. The low free diffusivity of pure C2F6 (D0=0.033 cm2/s) places it in a regime where the ADC measurement allows the surface-to-volume ratio to be determined in each voxel, a potentially valuable quantitative characterization of regional lung tissue destruction in emphysema.

Animals↗

PubMed2005

Feasibility of combining MR perfusion, angiography, and 3He ventilation imaging for evaluation of lung function in a porcine model.

RATIONALE AND OBJECTIVE: To assess the feasibility of combining magnetic resonance (MR) perfusion, angiography, and 3He ventilation imaging for the evaluation of lung function in a porcine model. MATERIALS AND METHODS: Fourteen consecutive porcine models with externally delivered pulmonary emboli and/or airway occlusions were examined with MR perfusion, angiography, and 3He ventilation imaging. Ultrafast gradient-echo sequences were used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast-agent injections. 2D multiple-section 3He imaging was performed subsequently via the inhalation of hyperpolarized 3He gas. The diagnostic accuracy of MR angiography for detecting pulmonary emboli was determined by two reviewers. The diagnostic confidence for different combinations of MR techniques was rated on the basis of a 5-point grading scale (5 = definite). RESULTS: The sensitivity, specificity, and accuracy of MR angiography for detecting pulmonary emboli were approximately 85.7%, 90.5%, and 88.1%, respectively. The interobserver agreement was very strong (k = 0.82). There was a clear tendency for confidence to increase when first perfusion and then ventilation imaging were added to the angiographic image (Wilcoxon signed ranks test, P = 0.03). CONCLUSION: The combination of the three methods of MR perfusion, angiography, and 3H ventilation imaging may provide complementary information on abnormal lung anatomy and function.

Administration, Inhalation↗

PubMed2005

3He diffusion MRI of the lung.

RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.

Diffusion Magnetic Resonance Imaging↗

PubMed2005

NMR detection of thermal damage in carbon fiber reinforced epoxy resins.

Composite materials of epoxy resins reinforced by carbon fibers are increasingly being used in the construction of aircraft. In these applications, the material may be thermally damaged and weakened by jet blast and accidental fires. The feasibility of using proton NMR relaxation times T1, T1rho, and T2 to detect and quantify the thermal damage is investigated. In conventional spectrometers with homogeneous static magnetic fields, T1rho is readily measured and is found to be well correlated with thermal damage. This suggests that NMR measurements of proton T1rho may be used for non-destructive evaluation of carbon fiber-epoxy composites. Results from T1rho measurements in the inhomogeneous static and RF magnetic fields of an NMR-MOUSE are also discussed.

Journal Article↗

PubMed2004

Magnetization tagging decay to measure long-range (3)He diffusion in healthy and emphysematous canine lungs.

Spatial modulation (tagging) of the longitudinal magnetization allows diffusive displacements to be measured over times approximately as long as T(1) and over correspondingly long distances. Magnetization tagging is used here with hyperpolarized (3)He gas in canine lungs with unilateral elastase-induced emphysema. A new scheme for analyzing images subsequent to tagging determines the spatially-resolved fractional modulation and its decay rate, using a sliding window. The diffusivity so determined over seconds and centimeter lengths, D(sec), is smaller in all cases than the diffusivity measured over milliseconds and hundreds of microns, D(msec) (in healthy lungs, this ratio is about 0.1). While D(msec) is sensitive to lung microstructure on the alveolar level, D(sec) reflects airway connectivity and provides new information on lung structure. The results show substantial increases in D(sec) in the lungs of four dogs with clear evidence of emphysema. For these dogs, the fractional increase in long-range diffusivity D(sec) in the emphysematous lungs was greater than that in short-range diffusivity D(msec).

Animals↗

PubMed2004

Hyperpolarized (3)He MRI of mouse lung.

Hyperpolarized (3)He images of mouse lung are presented. Ventilation images and measurements of (3)He apparent diffusion coefficient (ADC) are reported in healthy mice, and preliminary studies of emphysema and lung cancer in mice are described using these techniques. The design and operation of an electronically controlled small-animal ventilator to deliver the hyperpolarized gas and control animal respiration are described. Images are acquired using an asymmetric gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly diffusing (3)He. In mice with elastase-induced emphysema, the whole-lung average ADC is greater by approximately 25%, a statistically significant difference, compared to healthy animals. By contrast, mice exposed to cigarette smoke for up to 12 months reveal no statistically relevant increases in ADC, although emphysema was not confirmed in these mice. A study of lung cancer (melanoma) in mice is also presented. While tumors are shown to cause substantial ventilation defects in the lung, these defects appear confined to the cancerous regions and do not extend to large-scale regions of the lung distal to the tumors.

Animals↗

PubMed2004

Frequency shifts in parametrically enhanced low-field MR detection.

A high-amplitude, high-frequency readout field has previously been proposed for use with low-field MR. Because the resulting modulation sidebands are at higher frequencies than the low-field steady precession, improved detection sensitivity results. However, if the ac readout field is inhomogeneous, it will necessarily have transverse components resulting in frequency shifts and broadening of the MR signal. Numerical solutions of Bloch's equations are compared to the Bloch-Siegert result to assess the size of the frequency shifts. A formula is derived by the average Hamiltonian method and provides an excellent fit to the numerically obtained shifts.

Journal Article↗

PubMed2004

Feasibility of diffusion-NMR surface-to-volume measurements tested by calculations and computer simulations.

It has been demonstrated previously that the surface-to-volume ratio S/V can be determined from the derivative of the time-dependent diffusion coefficient D(t), in the limit t --> 0. Several questions arise concerning the practicality of determining S/V by NMR. In particular, how large are the errors generated by (1) working outside the t --> 0 limit and (2) measuring D outside the b --> 0 limit, both for narrow and full-width gradient pulses? Here b is gamma2G2delta2Delta for narrow pulses and gamma2G2t3/12 for broad pulses. These questions are addressed by random-walk computer simulations and numerical calculations in geometries relevant to small-airways of lung. The results demonstrate that one can work well outside the t --> 0 and b --> 0 limits, provided 10-20% accuracy in the measured S/V is sufficient. Emphasis is placed on the useful range of times t for which NMR determinations of lung S/V are feasible.

Algorithms↗

PubMed2004

Improved rejection of transmitter noise: a convenient scheme with resonant crossed diodes.

A method is presented for improved rejection of transmitter noise in the duplexer (transmit-receive switch). The capacitance of a set of crossed diodes forms a resonant circuit with a length of coaxial cable. The rejection of our resonant design is 60 dB, compared with only 12-15 dB for the usual method, all measured at 175 MHz. Tuning the entire duplexer to different frequencies is convenient, requiring only two new lengths of cable. The scheme is most useful with ungated linear rf power amplifiers at very high frequencies (above 100 MHz), where transmitter noise can be a severe problem.

Equipment Design↗

PubMed2003

Magnetic alignment in nominally non-magnetic hexagonal metal hydrides: NMR.

Powders of three hexagonal metal-hydrides or -deuterides are found to align in 4.4-8.3 T magnetic fields used for NMR. The field-alignment is unexpected, since all three systems have very small susceptibilities, as demonstrated by sharp NMR lines. The extent of alignment runs from nearly complete to barely detectable in ZrBe2(H,D)x, LuD3, and YD3, respectively. The preferred alignment direction in ZrBe2(H,D)x is with the crystallites' c-axis perpendicular to B, while the c-axis and B tend to be parallel in LuD3 and YD3. The susceptibilities chi parallel and chi perpendicular are determined from bulk magnetization measurements in aligned ZrBe2H1.4 powder. The alignment must be considered for proper analysis of NMR spectra in these and related materials.

Journal Article↗

PubMed2002

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI.

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Diffusion↗

PubMed2002

Combined MR proton lung perfusion/angiography and helium ventilation: potential for detecting pulmonary emboli and ventilation defects.

Three-dimensional (3D) perfusion imaging allows the assessment of pulmonary blood flow in parenchyma and main pulmonary arteries simultaneously. MRI using laser-polarized (3)He gas clearly shows the ventilation distribution with high signal-to-noise ratio (SNR). In this report, the feasibility of combined lung MR angiography, perfusion, and ventilation imaging is demonstrated in a porcine model. Ultrafast gradient-echo sequences have been used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast agent injections. 2D multiple-section (3)He imaging was performed subsequently by inhalation of 450 ml of hyperpolarized (3)He gas. The MR techniques were examined in a series of porcine models with externally delivered pulmonary emboli and/or airway occlusions. With emboli, perfusion deficits without ventilation defects were observed; airway occlusion resulted in matched deficits in perfusion and ventilation. High-resolution MR angiography can unambiguously reveal the location and size of the blood emboli. The combination of the three imaging methods may provide complementary information on abnormal lung anatomy and function.

Airway Obstruction↗