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Biomedical subjects

Mark D Does

Publications and source records attributed to Mark D Does.

9 recordsLinked to original sources

Temporal diffusion spectroscopy: theory and implementation in restricted systems using oscillating gradients.

The theory of temporal diffusion spectra is reviewed. In contrast to q-space spectroscopy, which measures the displacement spectrum of spins in a spatial domain, the spectral density of the velocity correlation function (VCF) in the temporal domain is considered. It is demonstrated that casting diffusion in this domain may facilitate measurements of microscopic geometry and the decomposition of the diffusion signal into components due to disperse flow and restricted diffusion. An oscillating gradient (OG) method of diffusion spectroscopy was developed and implemented. Microscopic pore sizes, surface-to-volume ratios (S/Vs), and diffusion path tortuosities were extracted from model systems using this method. Cases are discussed in which this type of experiment may allow the characterization of pore geometry when spatial domain experiments fail. OGs may be combined with imaging sequences to map complex patterns of diffusion and flow. Moreover, scalar apparent diffusion coefficient (ADC) measurements in complex biological systems may be subtly dependent on specific pulse sequence parameters. Thus, scalar ADC measurements using gradient pulses with different frequency spectra may give different results. Conversely, the frequency dependence of motion-sensitizing gradient pulses may be exploited to deduce the origin of ADC changes.

Diffusion Magnetic Resonance Imaging↗

Diffusion of myelin water.

We studied compartmentally specific characteristics of water diffusion in excised frog sciatic nerve by combining T1 or T2 selective acquisitions with pulse-gradient spin-echo (PGSE) diffusion weighting, with the specific objective of characterizing myelin water diffusion. Combining a PGSE with a Carr-Purcell-Meiboom-Gill (CPMG) acquisition provided apparent diffusion coefficients (ADCs) for each of the three T2 components found in nerve, including the short-lived component believed to be derived from myelin water. Double-inversion-recovery (DIR) preparation provided an alternate means of discriminating myelin water, and in combination with PGSE provided somewhat different measures of ADC. The DIR measures yielded myelin water ADCs of 0.37 microm2/ms (parallel to nerve) and 0.13 microm2/ms (perpendicular to nerve). These ADC estimates were postulated to be more accurate than those based on T2 discrimination, although the difference between the two findings is not clear.

Animals↗

Selective excitation of myelin water using inversion-recovery-based preparations.

T1 and T2 relaxation of excised frog sciatic nerve water was characterized at 7 T. Based on these findings, optimal timings for multiple inversion-recovery magnetization preparations were determined to selectively excite the so-called myelin-water T2 component. Subsequent double inversion-recovery and triple inversion-recovery preparations were used in combination with CPMG acquisitions to experimentally determine optimal timings and effect of the preparation. Using double inversion-recovery, optimal timings were found to excite magnetization that is predominantly (approximately 93%) derived from the myelin-water component. Greater selectivity (approximately 96%) was found by extending the preparation to triple inversion-recovery, at the price of decreasing SNR by a factor of approximately 2.

Animals↗

Relaxation-selective magnetization preparation based on T1 and T2.

A magnetization-preparation scheme is described that combines the spin-echo and inversion-recovery (SEIR) to select spins based on both T1 and T2 characteristics. The inclusion of T2 weighting allows for greater relative suppression of some tissues with respect to others, depending on their respective relaxation times, than does inversion-recovery alone. Formulae describing the observed magnetization following SEIR and double-SEIR (DSEIR) are presented with the corresponding formulae for inversion-recovery (IR) and double-IR (DIR). The formulae are validated with experimental studies on MnCl2 solutions and compared numerically for a variety of possible applications. Results indicate that DSEIR may yield 2x or more signal than DIR in some potential applications.

Chlorides↗

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

Animals↗

Compartmental study of T(1) and T(2) in rat brain and trigeminal nerve in vivo.

The integrated T(1)-T(2) characteristics of rat brain and trigeminal nerve water were studied in vivo using a rapid method for acquiring a series of images that depend on T(1) and T(2) relaxation times. Gray matter regions showed only one signal component in both the T(1) and T(2) domains. Trigeminal nerve, however, which has been shown previously to exhibit three T(2) components, was found to also exhibit three T(1) components. The correlations between these T(1) and T(2) components were demonstrated by uniquely filtering out each of the three T(2) components using an inversion-recovery preparation, as determined by the component T(1) values. Based on previous works, it is postulated that each of these three signal components is derived from a unique microanatomical region of the nerve. Knowledge of these T(1) components may thus prove valuable in devising novel methods of identifying the presence and quantifying the volume of tissue subtypes such as myelin.

Animals↗

Changes in CBF-BOLD coupling detected by MRI during and after repeated transient hypercapnia in rat.

The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption (CMRO(2)) remains incompletely understood. This study examined the relationship between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion-weighted (flow-sensitive alternating inversion recovery (FAIR)) MRI techniques both during induction of repeated transient hypercapnia (THC) and after return to normocapnia during whisker barrel functional activation. During induction of THC the FAIR signal became significantly elevated over control after 100 s of hypercapnia (P = 0.039), with a trend of increasing significance to 5 min (P = 0.000008). The FAIR signal in the activated cortex during subsequent normocapnia was significantly increased compared to pre-THC control after each successive period of THC. The mean grouped FAIR signal increased by 81% +/- 63% after one exposure (P = 0.021), by 163% +/- 55% after the second exposure (P = 0.0002), and by 240% +/- 54% after the third exposure (P = 0.000002). The mean grouped BOLD signal trended upward, but did not increase significantly during or after exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion-weighted from susceptibility imaging techniques, both in nonactivated cortex during hypercapnia, and with activation after multiple exposures to THC. These results are consistent with saturation of BOLD contrast as well as with increases in CMRO(2) with stimulation after multiple exposures to THC.

Animals↗

Differential gene expression in the kidney of sickle cell transgenic mice: upregulated genes.

The S+S-Antilles transgenic mouse used in this study has renal defects similar to those seen in sickle cell anemia patients: congested glomeruli, medullary fibrosis, renal enlargement, vasoocclusion, and a urine concentrating defect. We used gene expression microarrays to identify genes highly up-regulated in the kidneys of these mice and validated their expression by real-time PCR. Kidney hypoxia, as demonstrated by the presence of deoxyhemoglobin, was detected by blood oxygen dependent magnetic resonance imaging (BOLD-MRI). Some of the up-regulated genes included cytochrome P450 4a14, glutathione-S-transferase alpha-1, mitochondrial hydroxymethylglutaryl CoA synthase, cytokine inducible SH-2 containing protein, retinol dehydrogenase type III, arginase II, glycolate oxidase, Na/K ATPase, renin-1, and alkaline phosphatase 2. An increase in enzyme activity was also demonstrated for one of the up-regulated genes (arginase II). These genes can be integrated into several different pathophysiological processes: a hypoxia cascade, a replacement cascade, or an ameliorating cascade, one or all of which may explain the phenotype of this disease. We conclude that microarray technology is a powerful tool to identify genes involved in renal disease in sickle cell anemia and that the identification of various metabolic pathways may open new avenues for therapeutic interventions.

Anemia, Sickle Cell↗

Modified oscillating gradient pulses for direct sampling of the diffusion spectrum suitable for imaging sequences.

A variation of the oscillating gradient spin echo method had been developed, which isolates temporal frequencies of the dephasing spectrum. This allows sampling of the diffusion spectrum, the Fourier transform of the velocity correlation function (VCF). It has been shown that restriction and flow alter this function in ways that can be mathematically characterized, yielding quantitative information on restriction geometry and flow parameters. It is demonstrated that in many systems of interest, dispersion of velocity will produce a peak in the VCF spectrum near omega=0, while restricted diffusion will manifest itself in the spectrum at higher frequencies. The method, therefore, may be useful for decoupling their effects on the apparent diffusion coefficient (ADC), as well as in revealing the physics of both phenomena. This method has been implemented in model systems of packed beads, yielding data consistent with theoretical models of restricted diffusion spectra and data from one previous study. The method may have significant application to biology and medicine, as well as the study of transport phenomena in porous media and complex flow.

Diffusion↗