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We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils.

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The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized (3)He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized (3)He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation.

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We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.

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The pressure-volume (P-V) characteristics of the lung microcirculation are important determinants of the pattern of pulmonary perfusion and of red and white cell transit times. Using diffuse light scattering, we measured capillary P-V loops in seven excised perfused dog lobes at four lung volumes, from functional residual capacity (FRC) to total lung capacity (TLC), over a wide range of vascular transmural pressures (Ptm). At Ptm 5 cmH(2)O, specific compliance of the microvasculature was 8.6%/cmH(2)O near FRC, decreasing to 2.7%/cmH(2)O as lung volume increased to TLC. At low lung volumes, the vasculature showed signs of strain stiffening (specific compliance fell as Ptm rose), but stiffening decreased as lung volume increased and was essentially absent at TLC. The P-V loops were smooth without sharp transitions, consistent with vascular distension as the primary mode of changes in vascular volume with changes in Ptm. Hysteresis was small (0.013) at all lung volumes, suggesting that, although surface tension may set basal capillary shape, it does not strongly affect capillary compliance.

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Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.

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The large diffusion coefficients of gases result in significant spin motion during the application of gradient pulses that typically last a few milliseconds in most NMR experiments. In restricted environments, such as the lung, this rapid gas diffusion can lead to violations of the narrow pulse approximation, a basic assumption of the standard Stejskal-Tanner NMR method of diffusion measurement. We therefore investigated the effect of a common, biologically inert buffer gas, sulfur hexafluoride (SF(6)), on (129)Xe NMR and diffusion. We found that the contribution of SF(6) to (129)Xe T(1) relaxation in a 1:1 xenon/oxygen mixture is negligible up to 2 bar of SF(6) at standard temperature. We also measured the contribution of SF(6) gas to (129)Xe T(2) relaxation, and found it to scale inversely with pressure, with this contribution approximately equal to 1 s for 1 bar SF(6) pressure and standard temperature. Finally, we found the coefficient of (129)Xe diffusion through SF(6) to be approximately 4.6 x 10(-6) m(2)s(-1) for 1 bar pressure of SF(6) and standard temperature, which is only 1.2 times smaller than the (129)Xe self diffusion coefficient for 1 bar (129)Xe pressure and standard temperature. From these measurements we conclude that SF(6) will not sufficiently reduce (129)Xe diffusion to allow accurate surface-area/volume ratio measurements in human alveoli using time-dependent gas diffusion NMR.

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Changes in local pulmonary capillary blood volume (Vc) and oxygen saturation (S) have been difficult to measure in live animals. By utilizing the differences in absorption of light at two wavelengths (650 and 800 nm), we estimated the fractional change in Vc and S during the course of the cardiac cycle in eight anesthetized, ventilated rabbits at low and high lung volumes. Observations were made of the pattern of diffusely backscattered light, from an approximately 1-cm3 volume of lung illuminated with a point source placed on the pleural surface through a thoracotomy. At low lung volume, the fractional change in Vc was approximately 13%, the change in S was approximately 4.6%, and the mean S was close to 77%. The fluctuations in Vc and S lagged behind peak systemic blood pressure by about one-fifth and three-fifths of a cycle, respectively. At high lung volume, there were no important fluctuations in Vc or S, and the mean S was approximately 82%. These results are consistent with fluctuations in pulmonary capillary pressure and gas exchange over the cardiac cycle, and with decreasing capillary compliance with increasing lung volume.

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OBJECTIVE: To develop an instrument to help prevent pulmonary O2 toxicity, a syndrome that manifests itself in adult intensive care patients. METHODS: We designed, built, and tested a device that controls FIO2 exposure using oxygen saturation measured with a pulse oximeter (SpO2) in a negative feedback control system. A target SpO2 is designated by the clinician and the system adjusts the FIO2 from a mechanical ventilator so as to minimize the difference between the measured SpO2 and the target. Important elements of the system include a conservative artifact rejection algorithm, a gainscheduled sampled-data proportional-integral-derivative (PID) controller, and a safety system to prevent inspired mixtures with undesirably low FIO2 due to device failure. RESULTS: The control system was tuned in a series of animal experiments. Acceptable clinical response of the system was obtained using a gain-scheduled controller algorithm whereby the gain of the proportional term of a PID controller was adjusted based on the error signal and measured minute ventilation. Also, the artifact rejection algorithm and safety systems were successfully tested using simulation. CONCLUSIONS: Testing the effectiveness of this instrument will require comparison with manual control of FIO2 in an appropriately designed trial.

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Although changes in pulmonary function in parturients are documented, little is known about effects of regional anesthesia on these changes. This study was undertaken to determine if two local anesthetics, often used for epidural anesthesia for cesarean delivery, have different effects on pulmonary function testing. Nineteen ASA physical status I parturients undergoing elective cesarean delivery with epidural anesthesia were randomly assigned in double-blind fashion to receive either 0.5% bupivacaine or 2% lidocaine with epinephrine (1/200,000). Pulmonary function tests were measured using a calibrated spirometer with computer-recorded flow volume loops. Peak inspiratory pressure and peak inspiratory flow rate, peak expiratory pressure (PEP) and peak expiratory flow rate, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were measured. Measurements were taken prior to epidural placement and at T-10 and T-4 levels. Peak inspiratory pressure, FEV1/FVC, FEV1, FVC, peak expiratory flow rate, and peak inspiratory flow rate did not differ from baseline in either group. Patients receiving lidocaine showed a significantly greater decrease in PEP at both T-10 and T-4 levels. Pep is largely dependent on abdominal musculature. If a denser motor block is provided by 2% lidocaine with epinephrine than by 0.5% bupivacaine, these muscles would be more affected, resulting in a greater decrease in PEP. These results may have implications regarding choice of local anesthetic for epidural anesthesia in parturients with some degree of respiratory compromise undergoing cesarean delivery.

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Surgical procedures require correct identification of exposed anatomy with concomitant localization amidst contiguous structures. In endoscopic procedures the surgeon is provided a real-time endoscopic view and is prepared with radiologic images. Here we present an overview of a methodology of localization using intraoperatively acquired magnetic resonance (MR) images in preparation for magnetic resonance imaging-guided endoscopic sinus surgery. The methodology centers around a unique prototype imaging device and operating environment. An "open" 0.5 Tesla MR unit has been created that allows complete access to the patient's head and neck while concomitant images are obtained. Illustrative examples of localization technique from cadaver experiments are presented, as well as insights into the host of concerns for anesthesia, equipment, surgical instrumentation, communications, and documentation.

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PURPOSE: To describe new techniques for percutaneous biopsy with use of an open-configuration magnetic resonance (MR) imaging system with integrated frameless stereotaxic guidance tools. MATERIALS AND METHODS: In 28 patients, biopsy was performed in which the image plane was interactively controlled by the position of a hand-held probe attached to the biopsy needle. An icon integrated into the image was used to guide needle advancement in three planes orthogonal to the needle. In vitro measurements of spatial accuracy were also performed. RESULTS: Diagnostic tissue was retrieved in 25 of 28 patients. The system was most accurate near the isocenter with a maximum measured error of 3.1 mm within a sphere of radius 2.5 cm about the isocenter. CONCLUSION: MR-guided biopsy with a frameless stereotaxic technique is safe and accurate. Image feedback is near real time, and the procedure is interactive. These techniques may be used to perform MR-guided biopsies and to place probes for MR-guided therapies.

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STUDY OBJECTIVE: To describe the subjective experience and the physiologic effects of endotracheal intubation and complete neuromuscular block in unsedated humans. SETTING: Metropolitan V.A. Hospital. PATIENTS: 4 healthy, unsedated volunteers. INTERVENTIONS: Subjects' tracheas were intubated using topical anesthesia, then subjects were completely paralyzed with vecuronium and mechanically ventilated at various end-tidal partial pressure of carbon dioxide (PETCO2) levels, all without sedation. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR), blood pressure, oxygen saturation by pulse oximeter (SpO2), and PETCO2 were measured. Subjects' verbatim descriptions of their experiences and answers to systematic questions were recorded after the experiments. All subjects reported that tracheal intubation was a very unpleasant experience. None of the subjects found paralysis itself to be distressing, and it did not affect mentation. Subjects felt breathless when PETCO2 was even slightly elevated. HR was increased by intubation, but not by paralysis. All subjects reported sore throat, muscle aches, fever, and fatigue lasting up to 24 hours after the experiment. One subject experienced nausea and vomiting. Another subject experienced a sore throat that persisted for weeks due to a vocal cord ulcer, which resolved spontaneously. All subjects' SpO2 levels after the experiment were below their pre-experiment baselines. CONCLUSIONS: Our findings suggest that paralysis of healthy, knowledgeable, and psychologically well-prepared subjects for experimental purposes is feasible but may result in unpleasant, self-limiting after effects. Further, we conclude that, in any case of awake paralysis, close attention should be paid to arterial PCO2, adequate sedation and analgesia, minimization of pain during procedures, psychological support, and maintenance of communication when possible.

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Neuromuscular blocking agents are powerful drugs that are being used with increasing frequency in critical care medicine. The choice of a particular muscle relaxant is influenced by the patient's underlying condition and the side-effects of the drugs. Many factors influence an individual's response to neuromuscular blocking agents, and therefore, each patient's response should be monitored with a nerve stimulator. When muscle relaxants are used, common complications are patient awareness secondary to inadequate analgesia and sedation, and overdose of the neuromuscular blocking agents. Prolonged paralysis for days to weeks after the discontinuation of neuromuscular blocking agents is an uncommon but devastating complication, the etiology of which is poorly understood. Physicians in critical care medicine should receive formal training in the use of neuromuscular blocking drugs.

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It has been suggested that the act of taking a stride produces substantial respiratory volume displacement and that this assists the respiratory muscles during locomotion. We measured the flow at the mouth associated with stride in walking and running humans and found it to be 1-2% of respiratory tidal volume, which is too small to make an appreciable contribution to pulmonary ventilation.

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Wilson et al. (J. Appl. Physiol. 59:1924-28, 1985) have asserted that interdependence of regional expiratory flows could cause differences of interregional alveolar pressures to relax to time-independent limits during forced deflation. To test the hypothesis that such limiting differences do arise, we examined regional alveolar pressures during complete and partial maximally forced deflations of six excised canine lungs. Alveolar pressures were monitored using alveolar capsules on each of six lobes during forced deflations initiated at transpulmonary pressures of 30, 20, 15, and 10 cmH2O. In all lungs and in all maneuvers, interregional heterogeneity of alveolar pressure increased rapidly early in the deflation but much less so or not at all later in the deflation. When we compared complete with partial forced deflations, 16 of 24 maneuvers in six lungs showed clear evidence that as deflation progressed the degree of heterogeneity at isovolumic points became independent of the transpulmonary pressure from which the deflation was initiated. That is, alveolar pressures relaxed to limiting interregional differences that did not depend on time elapsed from the onset of the deflation. These data offer strong evidence of the existence of limiting differences. Such behavior implies that the sequence of regional emptying is controlled by a competition of opposing influences: nonuniformities of airway and parenchymal properties promoting nonuniformity of emptying vs. interdependence of regional expiratory flows promoting uniformity. As nonuniformity of regional pressures grows so do those factors that oppose that nonuniformity. These data underscore the insensitivity of maximum expiratory flow-volume curve configuration to the underlying inhomogeneous pattern of regional lung emptying.

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The tolerance of totally curarized subjects for prolonged breath hold is viewed by many as evidence that respiratory muscle contraction is essential to generate the sensation of breathlessness. Although conflicting evidence exists, none of it was obtained during total neuromuscular block. We completely paralyzed four normal, unsedated subjects with vecuronium (a non-depolarizing neuromuscular blocker). Subjects were mechanically ventilated with hyperoxic gas mixtures at fixed rate and tidal volume. End-expiratory PCO2 (PETCO2) was varied surreptitiously by changing inspired PCO2. Subjects rated their respiratory discomfort or 'air hunger' every 45 sec. At low PETCO2 (median 35 Torr) they felt little or no air hunger. When PETCO2 was raised (median 44 Torr) all subjects reported severe air hunger. They had reported the same degree of air hunger at essentially the same PETCO2 before paralysis. When questioned afterwards all subjects said the sensation could be described by the terms 'air hunger', 'urge to breathe', and 'shortness of breath', and that is was like breath holding. They reported no fundamental difference in the sensation before and after paralysis. We conclude that respiratory muscle contraction is not important in the genesis of air hunger evoked by hypercapnia.

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Anesthesia breathing circuit mechanics influence respiratory monitoring. Even when the magnitude of these effects is small, their presence may cause confusion and misinterpretation of information. Understanding the interactions between circuit mechanics and monitoring is critical in the design of new circuits and monitoring equipment, and important in their clinical use.

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The relationship between arterial oxygen saturation as measured by the pulse oximeter (SpO2) and the fractional arterial oxygen saturation (SaO2) in the presence and absence of carboxyhemoglobin (COHb) has been derived according to the theory of absorption spectroscopy. We find that our theoretically derived correction equation is similar to that found in the technical literature of Nellcor. However, the correction equations presented by Barker and Tremper and the technical literature of Ohmeda differ substantially from our equation when sufficient quantities of reduced hemoglobin are present and the fractional COHb saturation (SaCO) is high. Our approximated equation, derived from the Lambert-Beer law, is SaO2 = SpO2 (1 - 0.932 SaCO) + 0.032 SaCO. The equation of Barker and Tremper is SaO2 = SpO2 - 0.9 SaCO. The Nellcor equation is SaO2 = SpO2 (1 - SaCO).

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