Hyperpolarized 129 Xe MRI of the rat brain with chemical shift saturation recovery and spiral-IDEAL readout.

PURPOSE: To demonstrate the feasibility of 129 Xe chemical shift saturation recovery (CSSR) combined with spiral-IDEAL imaging for simultaneous measurement of the time-course of red blood cell (RBC) and brain tissue signals in the rat brain. METHODS: Images of both the RBC and brain tissue 129 Xe signals from the brains of five rats were obtained using interleaved spiral-IDEAL imaging following chemical shift saturation pulses applied at multiple CSSR delay times, τ. A linear fit of the signals to τ was used to calculate the slope of the signal for both RBC and brain tissue compartments on a voxel-by-voxel basis. Gas transfer was evaluated by measuring the ratio of the whole brain tissue-to-RBC signal intensities as a function of τ. To investigate the relationship between the CSSR images and gas transfer in the brain, the experiments were repeated during hypercapnic ventilation. RESULTS: Hypercapnia, affected the ratio of the tissue-to-RBC signal intensity (p = 0.026), consistent with an increase in gas transfer. CONCLUSION: CSSR with spiral-IDEAL imaging is feasible for acquisition of 129 Xe RBC and brain tissue time-course images in the rat brain. Differences in the time-course of the signal intensity ratios are consistent with gas transfer changes expected under hypercapnic conditions.

Hyperpolarized 129Xe magnetic resonance spectroscopy in a rat model of bronchopulmonary dysplasia.

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for noninvasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (Lm), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (tx), were compared with airspace mean axis length and area density (MAL and ρA) and percentage area of tissue and air (PTA and PAA) from histology. Lm was significantly larger in the exposed rats (P = 0.003) and correlated with MAL, ρA, PTA, and PAA (0.59<|ρ|<0.66 and P < 0.05). Observed increase in HCT (P = 0.012) and changes in tx are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

Effect of inhaled oxygen concentration on 129 Xe chemical shift of red blood cells in rat lungs.

PURPOSE: To investigate the dependence of dissolved 129 Xe chemical shift on the fraction of inhaled oxygen, Fi O2 , in the lungs of healthy rats. METHODS: The chemical shifts of 129 Xe dissolved in red blood cells, δRBC , and blood plasma and/or tissue, δPlasma , were measured using MRS in 12 Sprague Dawley rats mechanically ventilated at Fi O2 values of 0.14, 0.19, and 0.22. Regional effects on the chemical shifts were controlled using a chemical shift saturation recovery sequence with a fixed delay time. MRS was also performed at an Fi CO2 value of 0.085 to investigate the potential effect of the vascular response on δRBC and δPlasma . RESULTS: δRBC increased with decreasing Fi O2 (P = .0002), and δPlasma showed no dependence on Fi O2 (P = .23). δRBC at Fi CO2 = 0 (210.7 ppm ± 0.1) and at Fi CO2 = 0.085 (210.6 ppm ± 0.2) were not significantly different (P = .67). δPlasma at Fi CO2 = 0 (196.9 ppm ± 0.3) and at Fi CO2 = 0.085 (197.0 ppm ± 0.1) were also not significantly different (P = .81). CONCLUSION: Rat lung δRBC showed an inverse relationship to Fi O2 , opposite to the relationship previously demonstrated for in vitro human blood. Rat lung δRBC did not depend on Fi CO2 .

Application of a stretched-exponential model for morphometric analysis of accelerated diffusion-weighted 129Xe MRI of the rat lung.

OBJECTIVE: Diffusion-weighted, hyperpolarized 129Xe MRI is useful for the characterization of microstructural changes in the lung. A stretched exponential model was proposed for morphometric extraction of the mean chord length (Lm) from diffusion-weighted data. The stretched exponential model enables accelerated mapping of Lm in a single-breathhold using compressed sensing. Our purpose was to compare Lm maps obtained from stretched-exponential model analysis of accelerated versus unaccelerated diffusion-weighted 129Xe MRI data obtained from healthy/injured rat lungs. MATERIAL AND METHODS: Lm maps were generated using a stretched-exponential model analysis of previously acquired fully sampled diffusion-weighted 129Xe rat data (b values = 0 … 110 s/cm2) and compared to Lm maps generated from retrospectively undersampled data simulating acceleration factors of 7/10. The data included four control rats and five rats receiving whole-lung irradiation to mimic radiation-induced lung injury. Mean Lm obtained from the accelerated/unaccelerated maps were compared to histological mean linear intercept. RESULTS: Accelerated Lm estimates were similar to unaccelerated Lm estimates in all rats, and similar to those previously reported (< 12% different). Lm was significantly reduced (p < 0.001) in the irradiated rat cohort (90 ± 20 µm/90 ± 20 µm) compared to the control rats (110 ± 20 µm/100 ± 15 µm) and agreed well with histological mean linear intercept. DISCUSSION: Accelerated mapping of Lm using a stretched-exponential model analysis is feasible, accurate and agrees with histological mean linear intercept. Acceleration reduces scan time, thus should be considered for the characterization of lung microstructural changes in humans where breath-hold duration is short.

Potential Mechanism of Dermal Wound Treatment With Preparations From the Skin Gel of Arabian Gulf Catfish: A Unique Furan Fatty Acid (F6) and Cholesta-3,5-Diene (S5) Recruit Neutrophils and Fibroblasts to Promote Wound Healing.

Preparations from Arabian Gulf catfish (Arius bilineatus, Val) epidermal gel secretion (PCEGS) effectively heal chronic wounds in diabetic patients. However, specific lipid components of PCEGS that are responsible for various aspects of wound healing are unknown. Here, we report for the first time that, i) a unique preparation containing only proteins and lipids (Fraction B, FB), derived from the PCEGS accelerated the healing of experimental dermal wounds in female rats (transdermal punch biopsy) in vivo. Histological analyses showed that topical treatment of these wounds with FB promoted the migration of fibroblasts, facilitated the production of extracellular matrix (collagen, fibronectin), induced capillary formation and recruitment of immune cells, and accelerated overall wound healing by day 4 (tested at 1, 2, 3, 4, and 10 days; n=15 for vehicle; n=15 for FB treatment), ii) the lipids responsible for different stages of wound healing were separated into a protein-free bioactive lipid fraction, Ft, which contained a few common long-chain fatty acids, a unique furan fatty acid (F6) and a cholesterol metabolite, cholesta-3,5-diene (S5). Ft (the partially purified lipid fraction of PCEGS), and F6 and S5 present in Ft, proved to be bioactive for wound healing in human dermal fibroblasts. Ft increased the production and extracellular deposition of collagen and fibronectin, ex vivo, iii) Ft and its subcomponents, pure F6 and S5, also promoted human dermal fibroblast migration into the scratch wound gaps, ex vivo, iv) Ft, F6, and S5 promoted the recruitment of neutrophils (Green fluorescence protein labeled) to the site of injury in the transected tailfins of transgenic zebrafish, in vivo, v) Ft, but not F6 or S5, promoted the regeneration of tissues at the wound site in the transgenic zebrafish tailfin, in vivo. Therefore, we conclude that lipid fraction Ft from PCEGS contains the components necessary to promote complete wound healing, and F6 and S5 are responsible for promoting fibroblast and neutrophil recruitment to the site of wounds.

Chemical shift of 129 Xe dissolved in red blood cells: Application to a rat model of bronchopulmonary dysplasia.

PURPOSE: To measure the chemical shift of hyperpolarized 129 Xe dissolved in the red blood cells(δRBC ) of a cohort of rats exposed to hyperoxia and intermittent hypoxia (IH) to mimic human bronchopulmonary dysplasia, and to investigate the effect of xenon-blood distribution time on δRBC . METHODS: δRBC was measured from spectra acquired using a chemical shift saturation recovery sequence from 15 Sprague-Dawley rats exposed to hyperoxia-IH and 10 age-matched control rats. Sensitization to the xenon-blood distribution time was achieved by varying the time between saturation pulses, τ. δRBC was compared with blood fraction measured by histology of the cohort and blood oxygenation measured directly using pulse oximetry following a hypoxic challenge in an identically exposed cohort. RESULTS: The mean δRBC in the hyperoxia-IH exposed rats was 0.55 ± 0.04 ppm lower than that of the healthy cohort (P = .0038), and this difference did not depend on τ (P = .996). The blood fraction of the exposed cohort was lower than that of the healthy cohort (P = .0397). Oximetry measurements showed that the baseline arterial oxygen saturation (Sa O2 ) of each cohort was not different (P = .72), but after a hypoxic challenge, the Sa O2 of the exposed cohort was lower than that of the healthy cohort (P = .003). CONCLUSION: δRBC is reduced in rats exposed to hyperoxia-IH compared with control rats. The change in δRBC is consistent with enhanced blood oxygen desaturation of the exposed cohort measured by pulse oximetry during a hypoxic challenge. This suggests that the observed change in δRBC reflects enhanced desaturation in the hyperoxia-IH exposed cohort compared with the healthy cohort.

Flexible polarimetric probe for 3 × 3 Mueller matrix measurements of biological tissue.

Polarimetry is a noninvasive method that uses polarised light to assess biophysical characteristics of tissues. A series of incident polarisation states illuminates a biological sample, and analysis of sample-altered polarisation states enables polarimetric tissue assessment. The resultant information can, for example, help quantitatively differentiate healthy from pathologic tissue. However, most bio-polarimetric assessments are performed using free-space optics with bulky optical components. Extension to flexible fibre-based systems is clinically desirable, but is challenging due to polarisation-altering properties of optical fibres. Here, we propose a flexible fibre-based polarimetric solution, and describe its design, fabrication, calibration, and initial feasibility demonstration in ex vivo tissue. The design is based on a flexible fibre bundle of six multimode optical fibres, each terminated with a distal polariser that ensures pre-determined output polarisation states. The resultant probe enables linear 3 × 3 Mueller matrix characterization of distal tissue. Potential in vivo Mueller matrix polarimetric tissue examinations in various directly-inaccessible body cavities are envisioned.

Texture analysis of optical coherence tomography speckle for characterizing biological tissues in vivo.

We demonstrate a method for differentiating tissue disease states using the intrinsic texture properties of speckle in optical coherence tomography (OCT) images of normal and tumor tissues obtained in vivo. This approach fits a gamma distribution function to the nonlog-compressed OCT image intensities, thus allowing differentiation of normal and tumor tissues in an ME-180 human cervical cancer mouse xenograft model. Quantitative speckle intensity distribution analysis thus shows promise for identifying tissue pathologies, with potential for early cancer detection in vivo.

Noninvasive in vivo structural and vascular imaging of human oral tissues with spectral domain optical coherence tomography.

A spectral domain optical coherence tomography (SD-OCT) system and an oral imaging probe have been developed to visualize the microstructural morphology and microvasculature in the human oral cavity. Structural OCT images of ex vivo pig oral tissues with the histology of the same sites were acquired and compared for correlations. Structural in vivo OCT images of healthy human tissue as well as a pathologic site (ulcer) were obtained and analyzed based on the results of the ex vivo pig study, drawing on the similarity between human and swine oral tissues. In vivo Doppler and speckle variance OCT images of the oral cavity in human volunteers were also acquired, to demonstrate the feasibility of microvascular imaging of healthy and pathologic (scar) oral tissue.