Multi-mode heterodyne laser interferometry realized via software defined radio.

The agile generation and control of multiple optical frequency modes combined with the realtime processing of multi-mode data provides access to experimentation in domains such as optomechanical systems, optical information processing, and multi-mode spectroscopy. The latter, specifically spectroscopy of spectral-hole burning (SHB), has motivated our development of a multi-mode heterodyne laser interferometric scheme centered around a software-defined radio platform for signal generation and processing, with development in an entirely open-source environment. A challenge to SHB is the high level of shot noise due to the laser power constraint imposed by the spectroscopic sample. Here, we have demonstrated the production, detection, and separation of multiple optical frequency modes to the benefit of optical environment sensing for realtime phase noise subtraction as well as shot noise reduction through multi-mode averaging. This has allowed us to achieve improved noise performance in low-optical-power interferometry. Although our target application is laser stabilization via SHB in cryogenic temperature rare-earth doped crystals, these techniques may be employed in a variety of different contexts.

Parallel phase modulation scheme for interferometric gravitational-wave detectors.

Advanced LIGO (aLIGO) requires multiple frequency sidebands to disentangle all of the main interferometer's length signals. This paper presents the results of a risk reduction experiment to produce two sets of frequency sidebands in parallel, avoiding mixed 'sidebands on sidebands'. Two phase modulation frequencies are applied to separate Electro-Optic Modulators (EOMs), with one EOM in each of the two arms of a Mach-Zehnder interferometer. In this system the Mach-Zehnder's arm lengths are stabilized to reduce relative intensity noise in the recombined carrier beam by feeding a corrective control signal back to the Rubidium Titanyl Phosphate (RTP) EOM crystals to drive the optical path length difference to zero. This setup's use of the RTP crystals as length actuators provides enough bandwidth in the feedback to meet arm length stability requirements for aLIGO.

Noise characterization for resonantly enhanced polarimetric vacuum magnetic-birefringence experiments.

In this work we present data characterizing the sensitivity of the Biréfringence Magnetique du Vide (BMV) instrument. BMV is an experiment attempting to measure vacuum magnetic birefringence (VMB) via the measurement of an ellipticity induced in a linearly polarized laser field propagating through a birefringent region of vacuum in the presence of an external magnetic field. Correlated measurements of laser noise alongside the measurement in the main detection channel allow us to separate measured sensing noise from the inherent birefringence noise of the apparatus. To this end, we model different sources of sensing noise for cavity-enhanced polarimetry experiments, such as BMV. Our goal is to determine the main sources of noise, clarifying the limiting factors of such an apparatus. We find our noise models are compatible with the measured sensitivity of BMV. In this context, we compare the phase sensitivity of separate-arm interferometers to that of a polarimetry apparatus for the discussion of current and future VMB measurements.

Study of factors that may condition scintigraphic detection of venous thrombi and pulmonary emboli with indium-111-labeled platelets.

Incorporation of indium-111-labeled platelets (In-111-P) into venous thrombi and pulmonary emboli may permit rapid detection of these thromboemboli by gamma imaging. In a series of dogs in which femoral-vein thromboses and/or pulmonary embolism were induced experimentally by stasis and small amounts of thrombin, we addressed several questions pertinent to the sensitivity, specificity, and potential applicability of this approach. We found that when In-111-P were injected intravenously before thrombus induction or embolus release, femoral-thrombus images were consistently detectable within 15 min, whereas control femoral-vein images were unremarkable. Pulmonary emboli were also promptly imaged, and such In-111-P images agreed well with defects on Tc-99m MAA perfusion scans. When thrombi were aged in vivo for up to 10 hr after formation, they could still be imaged within 20-90 min after In-111-P injection. Administration of heparin, as an initial bolus followed by constant infusion, blocked platelet deposition on femoral-vein thrombi as assessed by both thrombus-to-blood ratios and failure to image. Injection of protamine at 6 hr, however, resulted in prompt thrombus imaging. These data indicate that this approach may well have applicability to the detection of thromboemboli in humans, since imaging remains possible in canine thrombi aged in vivo for 10 hr so long as heparin therapy has not been instituted. The dose of heparin required to inhibit imaging is not known. However, if these data prove comparable in humans, they suggest that imaging of thromboemboli could be achieved so promptly that only modest delay in the institution of heparin therapy would be required.

Humoral and cell-mediated immunity in peripheral blood following introduction of antigen into the middle ear.

Serum levels of specific IgG and the sensitization of peripheral blood T-lymphocytes were measured in guinea pigs after single-dose antigenic sensitization by two routes: intratympanic and intradermal injection. Keyhole limpet hemocyanin (KLH) served as the antigen. Intratympanic injection of antigen resulted in much lower levels of circulating anti-KLH IgG than intradermal injection. When KLH was conjugated with alum to produce nonspecific inflammation and serve as adjuvant, the intratympanic route was considerably enhanced, but remained much less effective than the intradermal route. Development of an IgG response was also somewhat less rapid following intratympanic than following intradermal administration. Marked sensitization of circulating T-lymphocytes was seen after intradermal injection of alum-precipitated KLH. A much weaker, though still positive, response was seen after intradermal injection of KLH alone and with the intratympanic injection of alum-precipitated KLH. No T-lymphocyte sensitization could be detected after intratympanic injection of KLH alone. It was concluded that the afferent limb of both humoral (IgG) and cell-mediated immunity was operative in the middle ear. Therefore, the middle ear does not represent an immunologically "privileged" site. On the other hand, the afferent limb from the middle ear appears to operate less effectively and rapidly than that from the dermis. This observation is consistent with observations in other mucosal systems.

Patterns of pulmonary perfusion scans in normal subjects.

A vital factor conditioning the usage of the pulmonary perfusion (Q) scan in the evaluation of patients suspected of pulmonary embolism is the prevalence of abnormal Q scans in subjects free of cardiopulmonary disease. Because this prevalence has not been well defined, we performed Q scans in 80 nonsmoking subjects 18 to 29 yr of age having no known active cardiopulmonary disease. Each subject underwent a history, physical examination, electrocardiogram, spirometry, and PA chest roentgenogram, followed by a 6-view Q scan. Two subjects in whom a Q defect was suspected underwent a 133Xe equilibrium-washout ventilation (V) scan. All Q scans were interpreted blindly and independently by 2 experienced readers. Seventy-nine of the 80 Q scans were read as normal. No subject demonstrated a lobar or segmental defect. One of the 80 subjects, who had a mild pectus excavatum, had a left upper lobe subsegmental defect, which was not seen on the V scan. Based on the statistical analysis of these data, no more than 3.68% of normal nonsmoking persons in this age group may have a lobar or segmental Q scan defect and no more than 6.77% may have a subsegmental defect (with 95% confidence). Therefore, our study indicated that Q scan defects, particularly lobar or segmental, are rarely present among normal nonsmokers in this age group.

Identification of pulmonary emboli in the dog: comparison of angioscopy and perfusion scanning.

Fifteen dogs were studied by perfusion scan, angioscopy and autopsy. In 10, emboli were formed in leg veins and released before study; five dogs were not embolized and served as controls. In controls, angioscopy disclosed no emboli, perfusion scans were normal after angioscopy and autopsy disclosed no emboli. Among the embolized dogs, 23 emboli were identified at autopsy. Perfusion scans disclosed 23 defects, but in three dogs there was a disparity between scan and autopsy localization. Angioscopy identified 21 of the 23 autopsy-defined emboli and localized them correctly; two emboli in vessels less than 1 mm in diameter were not visualized. Angioscopy may provide a useful new approach in animal investigations of pulmonary embolism and perhaps, after additional study, in selected patients.

Indium-111-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time.

The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of indium-111-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT.

Patterns of pulmonary perfusion scans in normal subjects.

The prevalence of abnormal pulmonary perfusion (Q) scans in persons without cardiopulmonary disease could condition the usefulness of the Q scan in the evaluation of patients in whom pulmonary embolism is suspected. In a recent study, we found that Q scan defects, particularly lobar or segmental defects, are rarely present in normal young nonsmokers. To determine if normal smokers of the same age group have a higher prevalence of Q defects, we performed 6 view Q scans in 40 subjects 18 to 29 yr of age who had no known active cardiopulmonary disease. Each subject had undergone a history, physical examination, electrocardiogram, spirometry, and posteroanterior chest roentgenogram prior to scanning. All Q scans were interpreted blindly and independently by 2 experienced readers. None of the 40 subjects was found to have an abnormal Q scan defined as the presence of a lobar, segmental, or subsegmental defect on 2 views. When these data were compared with our previous study, statistical analysis found no difference in the prevalence of abnormal Q scans in the 2 groups. We conclude that among young normal persons, abnormal Q scans are extremely uncommon and the prevalence of significant Q defects is not influenced by smoking.

Patterns of pulmonary perfusion scans in normal subjects. III. The prevalence of abnormal scans in nonsmokers 30 to 49 years of age.

The prevalence of abnormal pulmonary perfusion (Q) scans in persons without cardiopulmonary disease has not been well defined; this prevalence could impact on the current diagnostic approach to those in whom pulmonary embolic disease is suspected. In prior studies, we found that Q scan defects, particularly lobar or segmental defects, are rarely present in normal young smokers and nonsmokers. To determine if normal nonsmokers of an older age group have a higher prevalence of Q defects, we performed 6-view Q scans in 40 subjects 32 to 49 yr of age who had no known cardiopulmonary disease. Each subject had undergone a history, physical examination, electrocardiogram, spirometry, and posteroanterior chest roentgenogram prior to scanning. All Q scans were interpreted blindly and independently by 2 experienced readers. No subject demonstrated a lobar or segmental defect on 2 views. One subject with scoliosis had a subsegmental defect corresponding to a prominent aortic arch on the chest roentgenogram. We conclude that abnormal Q scans are extremely uncommon among normal nonsmokers 30 to 49 yr of age.

Distribution of ventilation in American alligator Alligator mississippiensis.

The regional distribution of ventilation in the multicameral lung of spontaneously ventilating alligators (Alligator mississippiensis) was studied with 133Xe scintigraphy. Frequent gamma camera images of 133Xe washin and washout were obtained and processed to allow evaluation of regional ventilation. Washin of 133Xe to equilibrium occurred in three to four breaths in anterior, central, and posterior compartments. Washin was most rapid in the posterior compartment and slowest in the anterior. The structure of the lungs and distribution of ventilation of inspired gas is consistent with the rapid radial spread of gas through a parallel arrangement of lung units surrounding the central intrapulmonary bronchus. Washout to equilibrium of 133Xe from all compartments occurred within three to four breaths. This rapid washin and washout of gas to all parts of the lung stands in contrast to the lungs of turtles and snakes, in which the caudal air sacs are relatively poorly ventilated.

Inhibition of indium-111 platelet accretion onto venous thrombi in dogs by prostacyclin.

The known platelet anti-aggregant effects of prostacyclin (epoprostenol) suggest that it may have therapeutic potential in conditions in which the platelet plays a pathophysiological role. The growth of venous thrombi is one such condition. We have attempted to determine, in a canine model of fresh venous thrombosis, whether prostacyclin infusion inhibits platelet accretion in vivo and how this in vivo event related to hemodynamic and in vitro platelet anti-aggregant effects. Gamma camera imaging over thrombi for accretion of indium-111-labeled platelets disclosed that prostacyclin, at an infusion rate of 50 ng/kg per min, inhibited platelet accretion in vivo and resulted in a 95 +/- 4% decrease in in vitro adenosine diphosphate-induced platelet aggregation, and a decrease in mean arterial pressure to 86 +/- 4% of pre-infusion values. Step-wise decrements of prostacyclin infusion demonstrated that platelet accretion occurred in vivo at infusion rates of approximately 10-20 ng/kg per min and correlated with an in vitro adenosine diphosphate-induced aggregation of 54 +/- 13% of control values. Thus, prostacyclin, in a dose that causes only a mild decrease in systemic pressure, can completely inhibit platelet uptake onto fresh venous thrombi in the dog, and this inhibition correlates closely with in vitro adenosine diphosphate-induced platelet aggregation. The potential therapeutic implications of these findings are discussed.

The in vivo behavior of granulocytes labeled with indium-111 in a canine model of pneumococcal pneumonia.

Use of [111In]granulocytes in the study of pulmonary inflammation requires study of their in vivo behavior. To study the pulmonary deposition of these cells and their ability to migrate from the capillary to the alveolus, we injected [111In]granulocytes into dogs 24 h after the induction of a right lower lobe pneumococcal pneumonia. Using external imaging, we found rapid clearance of [111In]granulocytes from the uninvolved lung (with a residual radioactivity of 24.5 +/- 4.2% at 4 h). In contrast, 83 +/- 12.4% of the initial radioactivity was present in inflamed lung at 4 h. Bronchoalveolar lavage fluid from the inflamed lung was more cellular than that from control lung, contained a greater fraction of polymorphonuclear leukocytes (82 +/- 4.1% versus 20 +/- 6.2%), and much greater cell-associated radioactivity (ratio of 423:1, inflamed to control). Autoradiography disclosed that this radioactivity was localized to consolidated alveoli and was not prominently distributed in arterioles or venules or in airways larger than 0.6 mm. We conclude that [111In]granulocytes are biologically active in the setting of acute lung inflammation.

Patterns of pulmonary perfusion scans in normal subjects. IV. The prevalence of abnormal scans in smokers 30 to 49 years of age.

The usefulness of ventilation-perfusion scans in the diagnosis of pulmonary embolism is limited by the wide range of pulmonary diseases that are associated with abnormal scans, and by the largely undetermined prevalence of abnormal scans in persons without cardiopulmonary disease. In prior studies, we found perfusion defects to be rarely present in young persons and in older nonsmokers. To determine if normal older smokers have a higher prevalence of abnormal ventilation and perfusion scans, we performed six-view 99mTc perfusion (Q) scans and 133Xe ventilation (V) scans in 40 subjects 30 to 49 yr of age who had no known cardiopulmonary disease. Each subject had undergone a history, physical examination, electrocardiogram, spirometry, and posteroanterior chest roentgenogram prior to scanning. All V and Q scans were interpreted blindly and independently by two experienced readers. No subject demonstrated a lobar or segmental defect on two views. One subject had a matched subsegmental defect, and one subject had delayed washout from a subsegmental area of the right upper lobe during V scanning, with a normal Q scan. We conclude that abnormal V and Q scans are uncommon among normal smokers 30 to 49 yr of age.

Lung mucociliary transport during high-frequency ventilation.

The effects of high-frequency, low-tidal-volume ventilation (HFV) and conventional intermittent positive-pressure ventilation (IPPV) on lung mucociliary transport were compared in 5 anesthetized, intubated mongrel dogs using a radioactive label. An aerosol of [99mTc]sulfur colloid was delivered to the dogs' airways and the subsequent clearance of isotope was followed over 4 h of either HFV or IPPV. After 4 h of IPPV, approximately 8 to 10% of the initial activity had cleared from the lung. By contrast, practically all the isotope remained in the lung after 4 h of HFV. Although the reasons for this were not definitely established in this study, several other observations were made that relate to this question. First, large amounts of mucus were visible in the trachea immediately after each of the 4-h HFV studies, whereas this was so in only one of the IPPV studies. Second, in 5 of 6 studies, a bolus of radioactive label placed on the posterior trachea after 4 h of HFV was noticed to disperse and move rapidly toward distal airways under the influence of HFV. Third, despite these findings of disturbed mucociliary transport during HFV, measurements of tracheal velocity, using a radioactive bolus technique during conventional ventilation, were the same after 4 h of HFV as after 4 h of IPPV (18.4 +/- 2.6 and 15.0 +/- 1.6 mm/min, respectively). We conclude that in the anesthetized dog HFV may alter mucociliary transport. This is unlikely to be the result of major structural damage to the mucosal surface, because tracheal mucous velocity measured after 4 h of HFV was not different from that after IPPV. It may be partly explained, however, by the retrograde flow of mucus that was observed during HFV in 5 of 6 studies.

Computer-assisted versus visual lung gallium-67 index in normal subjects and in patients with interstitial lung disorders.

The pulmonary uptake of 87Ga citrate has been proposed as an index that assists clinical decision-making in patients with certain interstitial lung diseases. Such use, however, requires definition of the range of normal values, the range of values in patients with various interstitial diseases, and interobserver and intraobserver variability. We studied 9 normal subjects and 15 patients with interstitial lung diseases. The 87Ga indexes were determined by visual analysis and by a computer-assisted method. We found that the variation among experienced observers in visual index values was substantial in both normal subjects and patients, and that the computer-assisted indexes were less variable. These data suggest that if this approach is to be used in clinical decision-making: (1) the variability of visual indexes, and of normal values, should be recognized; (2) consideration should be given to a less subjective, computer-assisted method of index calculation; (3) each institution should establish standardized methodology and consider determination of its range of variability and normal index values.