Wavelength-selective switch with direct few mode fiber integration.

The first realization of a wavelength-selective switch (WSS) with direct integration of few mode fibers (FMF) is fully described. The free-space optics FMF-WSS dynamically steers spectral information-bearing beams containing three spatial modes from an input port to one of nine output ports using a phase spatial light modulator. Sources of mode dependent losses (MDL) are identified, analytically analyzed and experimentally confirmed on account of different modal sensitivities to fiber coupling in imperfect imaging and at spectral channel edges due to mode clipping. These performance impacting effects can be reduced by adhering to provided design guidelines, which scale in support of higher spatial mode counts. The effect on data transmission of cascaded passband filtering and MDL build-up is experimentally investigated in detail.

Competitive advantage gained from the use of helicopter emergency medical services (HEMS) for trauma patients: Evaluation of 1724 patients.

OBJECTIVES: The aim of the study was to analyze helicopter emergency medical service (HEMS) in comparison to EMS, in respect to patient's mortality and morbidity. DESIGN: From a cohort of traumatized patients (n = 1724) prospectively enrolled in the German trauma registry (DGU-R) at Frankfurt University Hospital from 2009 to 2013, 1646 could be analyzed for in-hospital mortality and short-term outcome (GOS) at discharge and compared between HEMS and EMS. MEASUREMENTS AND MAIN RESULTS: 129 patients (7.8%) died in the hospital. Unadjusted mortality was significantly lower in the HEMS group compared to EMS (p = 0.001). In a multiple logistic regression analysis after adjustment of variables including reanimation and age as the strongest predictors, in-hospital mortality was significantly reduced in HEMS (p = 0.014, OR = 0.21). Further predictors in the multiple logistic regression analysis were GCS > = 8 (p = 0.001), RRsys (p < 0.001), ISS at Head/Neck > = 3 (p = 0.003), and total ISS > = 9 (p < 0.001). Total rescue time and on scene time were associated with mortality (p < 0.001) but not included in the multiple logistic regression model. Without adjustment, short-term outcome (GOS) was significantly improved (p = 0.014). In a linear model, after adjusting for multiple variables including age, ISS Head/Neck > = 3, ISS Extremities > = 3, GCS > = 8, and RRsys as the strongest predictors (p < 0.001), the association remained significant (p = 0.043). Further predictors in the multiple linear regression analysis were total ISS > = 9 (p = 0.002), ISS abdomen (p = 0.001), and ISS Chest (p = 0.011). CONCLUSIONS: A significant improvement for in-hospital survival for HEMS could be demonstrated. Especially in Germany, with a high number of secondary call outs (about 44%) after EMS has already reached the traumatized patient, HEMS must be the first choice for severely injured trauma patients. Dispatch criteria for immediate alarm of HEMS are recommended under practical considerations.

Synthesis of selenium-75 labeled tertiary diamines: new brain imaging agents.

Selenium-75 labeled tertiary diamines, bis[beta-(N,N-dimethylamino )ethyl] selenide (1), bis[beta-(N,N-diisopropylamino)ethyl] selenide (2), bis(beta-piperidinoethyl) selenide (3), and bis(beta-morpholinoethyl) selenide (4), were prepared by reducing [75Se]selenious acid with sodium borohydride and reacting the intermediate with the N,N-disubstituted aminoethyl chlorides. The effect of pH on lipid solubility (1-octanol/buffer distribution coefficient) was measured for each labeled compound. Biodistribution studies in rats showed high brain uptake for the tertiary diamines, especially for 3 and 4 (1.53 and 1.49% dose/organ, respectively, at 30 min after iv injection). The permanently charged bisquaternary amine, bis[beta-(N,N,N-trimethylammonio)ethyl] selenide (5), showed negligible brain uptake (0.06% dose/organ at 30 min).

Synthesis and tissue distribution study of iodine-labeled benzyl- and xylylamines.

Four iodine-125 labeled mono- and diamines were prepared and evaluated as potential brain-imaging agents. The diamines are analogues of the previously reported selenium-75 labeled diamines, which show high brain uptake and retention. All of the radioiodinated amines display high initial brain uptake in rats after intravenous injection (1.7-2.4% dose/organ). The xylylenediamines show prolonged brain retention (t1/2 approximately 18 h), which is desirable for brain imaging. In contrast, the benzylamine is rapidly cleared from brain tissue (t1/2 approximately 15 min).

Synthesis and biodistribution of 99mTc-labeled piperidinyl bis(aminoethanethiol) complexes: potential brain perfusion imaging agents for single photon emission computed tomography.

In developing clinically useful 99mTc-labeled radiopharmaceuticals for the evaluation of regional cerebral perfusion with single photon emission computed tomography (SPECT), a number of substituted alkyl(aryl)piperidinyl bis(aminoethanethiol) ligands for chelating [99mTc]TcO(III) were synthesized. Each ligand forms two diastereomers, syn and anti, after reacting with a racemic mixture of the ligand. The diastereomers were separated by high-pressure liquid chromatography. In biodistribution studies conducted in rats, the diastereomers exhibit widely disparate brain uptake values; however, this disparity seems to diminish as the steric bulk of the substituent at the C-4 position of the piperidinyl moiety increases. Furthermore, all the complexes evaluated failed to show a prolonged retention in the rat brain, suggesting that further structural modification may be necessary to obtain clinically useful complexes from this class of compounds.

Development of phosphonate derivatives of gadolinium chelates for NMR imaging of calcified soft tissues.

We have synthesized several classes of gadolinium (Gd) complexes for use as NMR contrast agents in the detection of soft-tissue calcification. Class I was made up of strongly chelated GdDTPA complexes with one carboxylate arm coupled to a phosphonate-containing molecule through an amide link. Class II complexes were formed by Gd with several aminophosphonates and phosphono carboxylic acids. Class III were Gd complexes of weak chelates containing no phosphonate. The calcium-seeking ability of each complex was assessed by in vivo bone uptake. Tissue distribution in normal rats showed that only the complexes of GdDTPA modified with a diphosphonate group and GdEDTMP (EDTMP is ethylenediaminetetrakis(methylenephosponate] showed adequate bone localization at the concentrations required for NMR contrast enhancement (approximately 20% of a 100 mumol/kg dose).

Synthesis of new bis(aminoethanethiol) (BAT) derivatives: possible ligands for 99mTc brain imaging agents.

In developing new brain perfusion imaging agents for single photon emission computed tomography (SPECT), five 99mTc-labeled neutral bis(aminoethanethiol) (BAT) derivatives capable of crossing the blood-brain barrier are reported. The five ligands are prepared by two versatile synthetic methods that can specifically introduce substituents on one of the carbons between two nitrogens. These ligands formed stable and neutral complexes with the reduced 99mTc, using either Sn(II) or sodium borohydride to reduce sodium [99mTc]pertechnetate. The biodistribution in rats was evaluated with [125I]iodoantipyrine, a freely diffusible tracer, as the internal reference. Compounds with a free hydroxyl group, 6 and 15, showed lower brain uptake. High initial brain uptake was observed for compounds 10 and 14, 1.28 and 2.30% dose/organ, respectively. Compounds of this type may be used as a basis for future structural modification to improve brain uptake and retention.

Effect of spatial distortion on anger camera field-uniformity correction: concise communication.

The field uniformity of a computer-assisted Anger-camera system, and the effect of field correction on quantitative data, have been studied. Our results show that the total counts of a source imaged across the crystal face varies with a s.d. of only 2.0%, but routine flood-field correction degrades the data to a s.d. of 9.4%. On the other hand, the area of a source 1.75 in. in diameter, imaged across the crystal face, varies with a s.d. of 9.7%. We conclude that the major source of field nonuniformity for an Anger camera is spatial distortion and not varying sensitivity across the crystal face.

The effect of window fraction on the deadtime of Anger cameras: concise communication.

The deadtime characteristics of an Anger camera are analyzed using a model consisting of a paralyzable front end and nonparalyzable display circuits. This model differs from previous deadtime analyses in that it considers the change in the fraction of counts passed by the pulse height analyzer as a function of the true count rate. Deadtime curves are analyzed for a Pho/Gamma IV Anger camera using 10%, 20%, and 35% windows.

Optimization of the gray scale for photoscanners: concise communication.

A gray scale providing easy visual interpretation of black-and-white photoscan transparencies was determined empirically from psychophysical studies conducted on 50 observers. This optimum gray scale provides equal visualization for equal countrate changes over the entire film range.

Charge and nature of technetium species produced in the reduction of pertechnetate by stannous ion.

By using a cation-exchange distribution technique, the net charge of the technetium species produced in the reduction of pertechnetate by stannous ion at ph less than or equal to 2 had been determined to be + 2. The species carrying this charge is either the dihydroxy technetate (Tc(OH)2(2)+) ion or the oxotechnetate (TcO2+) ion. These species are hydrolysed to technetium dioxide dihydrate (TcO2 - 2H2O) at higher pH.The advantage of the ion-exchange distribution technique for these studies is that they can be done with carrier-free technetium rather than at the high concentrations required for the more conventional methods of ion-charge determination. The results, therefore, are more likely to be applicable to the situation existing in the routine preparation of Tc-99m radiopharmaceuticals.

Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.

This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

Subcutaneous isoproterenol: a convenient rat model for early detection of myocardial necrosis.

The uptake of Tc-99m pyrophosphate was studied in rat myocardial lesions produced by a single subcutaneous injection of isoproterenol (10--50 mg/kg of body weight). The uptake in the whole heart of treated rats is directly proportional to the isoproterenol dose. The Tc-99m PPi uptake measured at various times after lesion initiation parallels the myocardial calcium concentration changes. This model is useful for screening radiopharmaceuticals, and may also be suitable for studying early uptake in myocardial infarcts.

A new brain perfusion imaging agent: [I-123]HIPDM:N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine.

Based on the pH-shift mechanism, a new brain imaging agent I-124 HIPDM (N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-[123I]iodobenzyl]-1,3-propanediamine ) has been developed. This agent can be prepared by a simple exchange reaction suitable for routine clinical use. The physicochemical parameters, partition coefficient vs. pH profile, and protein binding, as well as biodistribution in rats, were very similar to those of I-123 IMP (N-isopropyl-p-iodoamphetamine). High brain uptake was found in animals after i.v. injection. The brain radioactivity persists for at least 1 hr in rats and monkeys. Regional distribution in sections of rat brain appeared to reflect regional perfusion. In conjunction with single-photon emission tomography (SPECT), this agent may provide useful information on local cerebral perfusion in humans.

Effect of oxygen on the reduction of pertechnetate by stannous ion.

The effect of oxygen on the reduction of sodium pertechnetate by stannous chloride has been investigated using a paper electrophoresis method. It has been shown that oxygen interferes with the reduction process by oxidizing stannous ion, Sn(II), to stannic, Sn(IV), thereby leaving less Sn(II) available for the reduction of pertechnetate ion. In a solution of 1.66 X 13(-3)M TcO4- saturated with oxygen, a 3.4 molar ratio of Sn(II) to TcO4- was required for complete reduction of TcO4-, whereas in a nitrogen atmosphere, a 2.4 molar ratio was required for the same purpose. The oxygen interference increases as the concentration of TcO4- decreases. In a nitrogen atmosphere, 1.40 and 10.05 molar ratios of Sn(II) to TcO4- were required for the complete reduction of 1.66 X 10(-2)M and 1.66 X 10(-5)M TcO4- respectively. Once the reduction is accomplished, however, it is not easily reversible. Bubbling with oxygen for 1 hr had no effect on the quantity of reduced technetium.

Uptake of Tc-99m monophosphate complexes in bone and myocardial necrosis in animals.

Bidentate monophosphates--phosphonoacetate (PAA), 2-phosphonoproprionate (PPA), 2-methyl-2-phosphonoproprionate (MPPA), and carbamyl phosphate (CAP)--which are pyrophosphate analogs, were successfully labeled with Sn(II)-reduced [99mTc] pertechnetate in high yield (greater than 95%). Biodistribution studies show that these Tc-99m-labeled monophosphates do localize in bone. At 2 hr after injection, Tc-99m CAP has average femur uptakes of 1.9% in rats and 2.9% in rabbits, which correspond to calculated total-bone uptakes of 38% and 58%, respectively. These are comparable with the femur uptakes for Tc-99m methylene diphosphonate (MDP), which are 1.8% in rats and 2.7% in rabbits. However, the blood clearance rate for Tc-99m CAP was slower than that observed for Tc-99m MDP making the former less desirable for use as a bone-scanning agent. The femur uptakes for Tc99m PAA are 0.9% in rats and 1.2% in rabbits, corresponding to 18% and 24% in total bone, respectively. The PAA derivatives PPA and MPPA have much lower bone uptake. Technetium-99m CAP also concentrates in necrotic myocardium in rats, in amounts comparable to Tc-99m pyrophosphate.

Synthesis and biodistribution of neutral lipid-soluble Tc-99m complexes that cross the blood-brain barrier.

Three Tc-99m-labeled neutral 1,2-dithia-5,8-diazacyclodecane (BAT) chelates that are capable of crossing the blood-brain barrier (BBB) were prepared and evaluated. Biodistribution (i.v.) in rats showed a significant brain uptake (1-3%/whole brain) at 2 min. At 15 min the uptake dropped to about a tenth of the original level, indicating free passage in both directions across the BBB. Gamma camera images of a monkey confirmed the high initial brain uptake. This group of Tc-99m BAT compounds clearly exhibited in vivo stability and the ability to cross the BBB after an i.v. injection. Derivatives containing tertiary amine groups should have prolonged brain retention and might be suitable for SPECT studies of brain perfusion.

Effect of antidepressant and narcoleptic drugs on N-isopropyl p-iodoamphetamine biodistribution in animals.

N-isopropyl p-iodoamphetamine (IMP) demonstrates a high affinity for lung and brain during the first pass following intravenous injection. Its high brain affinity has been used to advantage for cerebral perfusion imaging, but the effects of drugs on IMP distribution could affect its utility. In this study, we determined the effects of the tricyclic antidepressant imipramine and the MAO inhibitors deprenyl and phenelzine on the biodistribution of IMP. We first determined the effect of loading dose and anesthesia on the biodistribution of IMP. In rats, biodistribution was not dependent on loading dose between 0.1 and 1.1 mg/kg. Anesthesia with thiopental and chloral hydrate depressed lung and brain IMP uptake. In rats, preloading doses of imipramine depressed lung uptake but did not result in increased brain IMP uptake; postloading doses of imipramine did not release IMP from the lung. In rabbits, simultaneous or postloading doses of imipramine resulted in release of IMP from the lung with an increase in brain activity. Both mixed A and B MAO inhibitors (phenelzine) and B selective MAO inhibitors (deprenyl) did not affect IMP distribution in rats. Based on the action of imipramine on IMP uptake and clearance in the lung, we postulate that IMP uptake and metabolism within the lung is related to the mixed function oxidase (MFO) system. As the lung is rich in the MFO system in humans, we would also predict from this study that IMP distribution in patients under antidepressant therapy would not be affected by either tricyclic or MAO inhibitor agents apart from the effect of these drugs on cerebral perfusion.

Technetium-99m bis (aminoethanethiol) complexes with amine sidechains--potential brain perfusion imaging agents for SPECT.

In an effort to develop new clinically useful technetium-99m bis(aminoethanethiol) ([99mTc]BAT) complexes for the evaluation of regional cerebral perfusion, two new BAT ligands containing amines in the sidechain were synthesized and subsequently complexed with 99mTc to yield the target complexes: [99mTc]DEA and [99mTc]TMPDA. Each complex was obtained as mixtures of two isomers, syn and anti, which were separated chromatographically. In biodistribution studies, both isomers of [99mTc]TMPDA showed little uptake in the brain. In contrast, the brain uptake values at 2 and 15 min for [99mTc]DEA-anti were 0.99 and 0.26, whereas, the corresponding values for DEA-syn were 2.27, 0.64% dose/organ, respectively. Autoradiographic studies (in rats) using both isomers of [99mTc]DEA show a fixed regional distribution and a higher concentration of radioactivity in the gray matter relative to the white matter. Planar imaging using [99mTc]DEA-syn clearly demonstrates localization of the complex in the brain with a T 1/2 of 41 min, suggesting some potential for use with single photon emission computed tomography.

Radiotracers for functional brain imaging.

The rapid growth of nuclear medicine 25 years ago was in large part related to the success of brain tumor imaging using radiopharmaceuticals designed to detect changes in the blood-brain barrier (BBB). The success of computed tomography, and more recently nuclear magnetic resonance, in imaging these lesions has all but eliminated the use of radioactive agents for brain tumor detection. But, in recent years there has been a new wave of interest in isotope studies of the brain. The recent emphasis has been on agents which enter the brain across the BBB and are designed to provide functional data ranging from regional perfusion and metabolism to the distribution of binding sites for neuroactive compounds. While none of these new radiopharmaceuticals has yet come into widespread clinical application, the research results already achieved clearly indicate that brain imaging will again be an important aspect of nuclear medicine practice.