Prototype of a Military Medic Smartphone Medical Graphical User Interface for Use by Medics in Deployed Environments.

INTRODUCTION: Prompt and effective combat casualty care is essential for decreasing morbidity and mortality during military operations. Similarly, accurate documentation of injuries and treatments enables quality care, both in the immediate postinjury phase and the longer-term recovery. This article describes efforts to prototype a Military Medic Smartphone (MMS) for use by combat medics and other health care providers who work in austere environments. MATERIALS AND METHODS: The MMS design builds on previous electronic health record systems and is based on observations of medic workflows. It provides several functions including a compact yet efficient physiologic monitor, a communications device for telemedicine, a portable reference library, and a recorder of casualty care data from the point of injury rearward to advanced echelons of care. Apps and devices communicate using an open architecture to support different sensors and future expansions. RESULTS: The prototype MMS was field tested during live exercises to generate qualitative feedback from potential users, which provided significant guidance for future enhancements. CONCLUSIONS: The widespread deployment of this type of device will enable more effective health care, limit the impact of battlefield injuries, and save lives.

Artificial Intelligence for the Future Radiology Diagnostic Service.

Radiology historically has been a leader of digital transformation in healthcare. The introduction of digital imaging systems, picture archiving and communication systems (PACS), and teleradiology transformed radiology services over the past 30 years. Radiology is again at the crossroad for the next generation of transformation, possibly evolving as a one-stop integrated diagnostic service. Artificial intelligence and machine learning promise to offer radiology new powerful new digital tools to facilitate the next transformation. The radiology community has been developing computer-aided diagnosis (CAD) tools based on machine learning (ML) over the past 20 years. Among various AI techniques, deep-learning convolutional neural networks (CNN) and its variants have been widely used in medical image pattern recognition. Since the 1990s, many CAD tools and products have been developed. However, clinical adoption has been slow due to a lack of substantial clinical advantages, difficulties integrating into existing workflow, and uncertain business models. This paper proposes three pathways for AI's role in radiology beyond current CNN based capabilities 1) improve the performance of CAD, 2) improve the productivity of radiology service by AI-assisted workflow, and 3) develop radiomics that integrate the data from radiology, pathology, and genomics to facilitate the emergence of a new integrated diagnostic service.

Deletion of Rap1 disrupts redox balance and impairs endothelium-dependent relaxations.

AIMS: Repressor activator protein 1 (Rap1) is conventionally known as a static structural component of the telomere, but recent evidence indicates that it exerts functions within and outside the nucleus taking part in metabolic regulation and promoting inflammatory responses. The present study investigated whether or not Rap1 deletion affects oxidative stress and nitric oxide (NO) bioavailability in the vascular wall, thus modulating endothelial function. METHODS AND RESULTS: Vascular responsiveness was studied in wire myographs in aortae from Rap1 wildtype and knockout mice. Deletion of Rap1 impaired endothelium-dependent relaxations elicited by acetylcholine. Rap1 deficiency did not affect the activation of endothelial NO synthase or the sensitivity of vascular smooth muscle to NO donors. The blunted acetylcholine-mediated relaxations in Rap1 deficient aortae were restored with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, apocynin or VAS2870. Rap1 deletion lowered cellular thiol-redox status and diminished activities of thiol-redox enzymes, thioredoxin 1 and glutaredoxin 1. CONCLUSIONS: The capacity of thioredoxin 1 and glutaredoxin 1 to reduce intra-protein disulfide bridges is weakened in Rap1 deficient mice, resulting in hyper-activation of NADPH oxidase and greater reactive oxygen species generation. The high oxidative stress in Rap1 deficient mice is implicated with greater oxidative breakdown of NO, explaining the blunted acetylcholine-mediated relaxations in this animal. These findings imply that Rap1 plays an unanticipated role in regulating the fate of NO (a pivotal determinant of vascular homeostasis) and thus identify a new physiological importance of the telomere-associated protein.

Blomia tropicalis allergen 5 (Blo t 5) T-cell epitopes and their ability to suppress the allergic immune response.

Blomia tropicalis is the major asthma allergen in the tropics comparable to Dermatophagoides pteronyssinus. However, little is known about the B. tropicalis epitopes recognized by T cells. Our aim was to identify the T-cell epitopes in the major B. tropicalis allergen, Blo t 5, and investigate the potential of the corresponding peptides to inhibit the allergic inflammatory lung response. C57BL/6 mice were immunized with plasmid DNA encoding Blo t 5 and T-cell epitopes identified using the interferon-γ ELISPOT assay with 15-mer overlapping peptides. C57BL/6 mice were sensitized with bone-marrow-derived dendritic cells (BMDC) pulsed with Blo t 5 allergen followed by intranasal Blo t 5 challenge. Two H-2b restricted epitopes (Bt576-90 and Bt5106-115 ) were recognized by CD4 T cells specific for Blo t 5, but no CD8 epitopes were identified. In mice sensitized with Blo t 5-pulsed BMDC and challenged with intranasal Blo t 5 Bt576-90 and Bt5106-115 , peptide-specific CD4 T cells were found to secrete the T helper type 2 cytokines interleukin-5 and interleukin-13. Intradermal administration of synthetic peptides encoding the identified T-cell epitopes suppressed allergic airway inflammation to further allergen challenges. Hence, we have identified novel CD4 T-cell epitopes specific for Blo t 5 and demonstrated that these peptides could be employed therapeutically to suppress the T-cell response in a murine model of allergic airway inflammation.

Priming with high and low respiratory allergen dose induces differential CD4+ T helper type 2 cells and IgE/IgG1 antibody responses in mice.

Sensitization of allergic patients normally takes place over several years and is the result of repeated exposure to low levels of allergen. Most mouse asthma models use a high dose of allergen administered over a short period. We have investigated the role of dose in the immune response to an inhaled respiratory allergen (Blomia tropicalis). We observed the effect of priming dose on the allergic response in mice intranasally immunized with low (0·5 µg) and high (50 µg) doses of B. tropicalis extract and killed 1 day after the last challenge. For both doses of allergen, T helper type 2 (Th2) cells and Th2 cytokines were evident as well as eosinophilic inflammation accompanied by mucus hyper-secretion. By contrast, IgE and IgG1 antibody responses were normally only detected at high-dose priming. To investigate the mechanism for these effects, we found group 2 innate lymphoid cells (ILC2s) were increased 48 hr after challenge in the low-dose-treated but not the high-dose-treated mice. Furthermore, we determined whether repeated low-dose exposure with different priming protocols could induce an antibody response. Repeated low-dose exposure to 0·5 µg three times weekly for 4 weeks (cumulative 6 µg) had the same effect as a shorter high-dose exposure (cumulative 80 µg) and increasing cumulative dose induced antibody responses. These data indicate that low doses of allergen are sufficient to prime Th2 cells and ILC2s, but insufficient to induce antibody responses. Cumulative exposure to small amounts of allergen induces both Th2 and antibody responses and may better reflect natural sensitization.

GM-CSF-licensed CD11b+ lung dendritic cells orchestrate Th2 immunity to Blomia tropicalis.

The Blomia tropicalis dust mite is prevalent in tropical and subtropical regions of the world. Although it is a leading cause of asthma, little is known how it induces allergy. Using a novel murine asthma model induced by intranasal exposure to B. tropicalis, we observed that a single intranasal sensitization to B. tropicalis extract induces strong Th2 priming in the lung draining lymph node. Resident CD11b(+) dendritic cells (DCs) preferentially transport Ag from the lung to the draining lymph node and are crucial for the initiation of Th2 CD4(+) T cell responses. As a consequence, mice selectively deficient in CD11b(+) DCs exhibited attenuated Th2 responses and more importantly did not develop any allergic inflammation. Conversely, mice deficient in CD103(+) DCs and CCR2-dependent monocyte-derived DCs exhibited similar allergic inflammation compared with their wild-type counterparts. We also show that CD11b(+) DCs constitutively express higher levels of GM-CSF receptor compared with CD103(+) DCs and are thus selectively licensed by lung epithelial-derived GM-CSF to induce Th2 immunity. Taken together, our study identifies GM-CSF-licensed CD11b(+) lung DCs as a key component for induction of Th2 responses and represents a potential target for therapeutic intervention in allergy.

Gamma interferon regulates contraction of the influenza virus-specific CD8 T cell response and limits the size of the memory population.

The factors that regulate the contraction of the CD8 T cell response and the magnitude of the memory cell population against localized mucosal infections such as influenza are important for generation of efficient vaccines but are currently undefined. In this study, we used a mouse model of influenza to demonstrate that the absence of gamma interferon (IFN-γ) or IFN-γ receptor 1 (IFN-γR1) leads to aberrant contraction of antigen-specific CD8 T cell responses. The increased accumulation of the effector CD8 T cell population was independent of viral load. Reduced contraction was associated with an increased fraction of CD8 T cells expressing the interleukin-7 receptor (IL-7R) at the peak of the response, resulting in enhanced numbers of memory/memory precursor cells in IFN-γ(-/-) and IFN-γR(-/-) compared to wild-type (WT) mice. Blockade of IL-7 within the lungs of IFN-γ(-/-) mice restored the contraction of influenza virus-specific CD8 T cells, indicating that IL-7R is important for survival and is not simply a consequence of the lack of IFN-γ signaling. Finally, enhanced CD8 T cell recall responses and accelerated viral clearance were observed in the IFN-γ(-/-) and IFN-γR(-/-) mice after rechallenge with a heterologous strain of influenza virus, confirming that higher frequencies of memory precursors are formed in the absence of IFN-γ signaling. In summary, we have identified IFN-γ as an important regulator of localized viral immunity that promotes the contraction of antigen-specific CD8 T cells and inhibits memory precursor formation, thereby limiting the size of the memory cell population after an influenza virus infection.

NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms.

An effective immune response against influenza A infection depends on the generation of virus-specific T cells. NK cells are one of the first-line defenses against influenza A infection. We set out to delineate the role of NK cells in T cell immunity using a murine model of influenza A infection with A/PR/8/34. We show that early T cell recruitment mainly occurs in the posterior mediastinal lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic cell (DC) and T cell recruitment into the pMLN. A similar reduction of T cell recruitment was observed when migration was blocked by pertussis toxin, suggesting that migration of pulmonary NK cells and DCs regulates cell recruitment to the pMLN. T cell recruitment was dependent on IFN-γ, and transfer of IFN-γ-competent naive NK cells into IFN-γ-/- mice restored T cell recruitment, whereas IFN-γ-deficient NK cells failed to do so. In addition, NK cell depletion reduced the uptake and transport of influenza A virus by DCs, and significantly impaired the virus-specific T cell response. Both IFN-γ-/- and perforin-/- mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-γ and perforin. In summary, our data suggest that NK cells play a critical role in the initiation and shaping of the T cell response after influenza A infection.

Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function.

BACKGROUND: Previous studies have shown that CD8 T cells can both prevent and cause allergic responses. However, the underlying mechanisms remain to be elucidated. OBJECTIVE: We aim to investigate the potential of CD8 T cells with different IFN-γ expressions to modulate the elicitation of allergic inflammation following ovalbumin (OVA) challenge and investigate the underlying mechanisms. METHODS: To study the role of IFN-γ in the effect of CD8 T cells, effector CD8 T cells from CD8 OVA transgenic (OT-I) mice and IFN-γ(-/-)OT-I mice were transferred to OVA-sensitized mice the day before 3 challenges with OVA. The effect on lung dendritic cells (DCs) exerted by CD8 T cells was studied with ex vivo culture of sorted DCs from treatment mice with CD4 T cells. RESULTS: Effector OT-I, but not IFN-γ(-/-)OT-I CD8 T cells, attenuated eosinophilia and mucus secretion in the lungs of sensitized mice in an antigen-specific manner. Effector IFN-γ(-/-)OT-I CD8 T cells displayed a Tc2-/Tc17-biased phenotype with weaker cytotoxicity and were able to both induce and exacerbate eosinophilia as well as neutrophilia. OT-I CD8 T cells increased the ability of lung CD11b(+)CD103(-) DCs to both prime the differentiation of naive OVA-specific CD4 T cells toward a T(H)1 phenotype and enhance IFN-γ production by antigen-experienced lung CD4 T cells. CONCLUSION: Effector CD8 T cells attenuate pulmonary inflammation and alter the ability of DCs within the allergic lung to polarize T cells to a T(H)1 phenotype during a T(H)2 response. In the absence of IFN-γ, CD8 T cells assume a Tc2-/Tc17-biased phenotype and potentiate inflammation.

Background and Mathematical Analysis of Diffusion MRI Methods.

The addition of a pair of magnetic field gradient pulses had initially provided the measurement of spin motion with nuclear magnetic resonance (NMR) techniques. In the adaptation of DW-NMR techniques to magnetic resonance imaging (MRI), the taxonomy of mathematical models is divided in two categories: model matching and spectral methods. In this review, the methods are summarized starting from early diffusion weighted (DW) NMR models followed up with their adaptation to DW MRI. Finally, a newly introduced Fourier analysis based unifying theory, so-called Complete Fourier Direct MRI, is included to explain the mechanisms of existing methods.

Imaging components for a robotic casualty evaluation system.

Combat medics have a vital role in the protection of wounded soldiers in the battlespace. However, their duties expose them to great risks. Furthermore, these medics are a limited resource and must be carefully tasked in order to provide maximum benefit to their units. For these reasons, we are applying the American GNC Corporation's (AGNC) Coremicro(R) Robotic System for autonomous evaluation of battlefield casualties. These robots are intended to navigate to a casualty, determine his/her overall health status, and perform limited diagnostic imaging in order to assess the presence of injuries that would prevent or complicate extraction. In this paper, we describe development work on some of the key components of the proposed robotic system, namely the overall concept of operations (ConOps) and initial testing of infrared and ultrasound imaging cameras. When fully deployed, this system will act as a medical force multiplier, enabling improved care of wounded soldiers and protecting the health and safety of military medical personnel.

Industry roundtable for interoperability and business process.

Healthcare challenges for the military are becoming increasingly complex and the solution to these challenges lies in effective collaboration between industry, government, and academia. Creating and maintaining such collaboration will require political, management, technical, and financial support. This article summarizes a discussion held during the National Forum on the Future of the Defense Health Information System which focused on the best methods for achieving this collaboration and any particular unique roadblocks facing this effort.

Blast-related brain injury: imaging for clinical and research applications: report of the 2008 st. Louis workshop.

Blast-related traumatic brain injury (bTBI) and post-traumatic stress disorder (PTSD) have been of particular relevance to the military and civilian health care sectors since the onset of the Global War on Terror, and TBI has been called the "signature injury" of this war. Currently there are many questions about the fundamental nature, diagnosis, and long-term consequences of bTBI and its relationship to PTSD. This workshop was organized to consider these questions and focus on how brain imaging techniques may be used to enhance current diagnosis, research, and treatment of bTBI. The general conclusion was that although the study of blast physics in non-biological systems is mature, few data are presently available on key topics such as blast exposure in combat scenarios, the pathological characteristics of human bTBI, and imaging signatures of bTBI. Addressing these gaps is critical to the success of bTBI research. Foremost among our recommendations is that human autopsy and pathoanatomical data from bTBI patients need to be obtained and disseminated to the military and civilian research communities, and advanced neuroimaging used in studies of acute, subacute, and chronic cases, to determine whether there is a distinct pathoanatomical signature that correlates with long-term functional impairment, including PTSD. These data are also critical for the development of animal models to illuminate fundamental mechanisms of bTBI and provide leads for new treatment approaches. Brain imaging will need to play an increasingly important role as gaps in the scientific knowledge of bTBI and PTSD are addressed through increased coordination, cooperation, and data sharing among the academic and military biomedical research communities.

Locating and targeting moving tumors with radiation beams.

The current climate of rapid technological evolution is reflected in newer and better methods to modulate and direct radiation beams for cancer therapy. This Vision 20/20 paper focuses on part of this evolution, locating and targeting moving tumors. The two processes are somewhat independent and in principle different implementations of the locating and targeting processes can be interchanged. Advanced localization and targeting methods have an impact on treatment planning and also present new challenges for quality assurance (QA), that of verifying real-time delivery. Some methods to locate and target moving tumors with radiation beams are currently FDA approved for clinical use-and this availability and implementation will increase with time. Extensions of current capabilities will be the integration of higher order dimensionality, such as rotation and deformation in addition to translation, into the estimate of the patient pose and real-time reoptimization and adaption of delivery to the dynamically changing anatomy of cancer patients.

Predominance of subtype 3 among Blastocystis isolates from a major hospital in Singapore.

Blastocystis is an enteric protozoan parasite commonly found in humans and animals. Phylogenetic and genotypic analyses have shown that Blastocystis exhibits extreme genetic diversity, and humans are host to a number of zoonotic isolates. In the present study, the prevalence of Blastocystis in 276 stool samples from a hospital in Singapore was examined, and for the first time, riboprinting using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genetic diversity of the Blastocystis isolated from the Singapore population. The prevalence rate was determined to be 3.3% (9/276), and Blastocystis displaying two main ribotypes were isolated. As a comparison, we performed PCR-RFLP using two different published methodologies, and both methods allowed the isolates to be divided into two distinct groups based on their riboprint patterns. According to a recently proposed classification scheme, 78% (7/9) of the isolates were of subtype 3, while 22% (2/9) were subtype 1. The predominance of subtype 3 in an urbanized city state such as Singapore is in agreement with the idea that subtype 3 is a genotype of human origin.

Geometric accuracy of a real-time target tracking system with dynamic multileaf collimator tracking system.

PURPOSE: Dynamically compensating for target motion during radiotherapy will increase treatment accuracy. A laboratory system for real-time target tracking with a dynamic MLC has been developed. In this study, the geometric accuracy limits of this DMLC target tracking system were evaluated. METHODS AND MATERIALS: A motion simulator was programmed to follow patient-derived tumor motion paths, parallel to the leaf motion direction. A target attached to the simulator was optically tracked, and the leaf positions adjusted to continually align the DMLC beam aperture to the target. Analysis of the tracking accuracy was based on video images of the target and beam alignment. The system response time was determined and the tracking error measured. Response time-corrected tracking accuracy was also calculated to investigate the accuracy limits of an improved system. RESULTS: The response time of the system is 160 +/- 2 ms. The geometric precision for tracking patient motion is 0.6 to 1.1 mm (1 sigma) for the 3 patient datasets tested, with tracking errors relative to the original patient motion of 35, 40, and 100%. CONCLUSIONS: A DMLC target tracking system has been developed that can account for detected motion parallel to the leaf motion direction. The tracking error has a negligible systematic component. Reducing the response time will further increase the overall system accuracy.

Progress in SPECT/CT imaging of prostate cancer.

Prostate cancer is the most common type of cancer (other than skin cancer) among men in the United States. Although prostate cancer is one of the few cancers that grow so slowly that it may never threaten the lives of some patients, it can be lethal once metastasized. Indium-111 capromab pendetide (ProstaScint, Cytogen Corporation, Princeton, NJ) imaging is indicated for staging and recurrence detection of the disease, and is particularly useful to determine whether or not the disease has spread to distant metastatic sites. However, the interpretation of 111In-capromab pendetide is challenging without correlated structural information mostly because the radiopharmaceutical demonstrates nonspecific uptake in the normal vasculature, bowel, bone marrow, and the prostate gland. We developed an improved method of imaging and localizing 111In-Capromab pendetide using a SPECT/CT imaging system. The specific goals included: i) development and application of a novel iterative SPECT reconstruction algorithm that utilizes a priori information from coregistered CT; and ii) assessment of clinical impact of adding SPECT/CT for prostate cancer imaging with capromab pendetide utilizing the standard and novel reconstruction techniques. Patient imaging studies with capromab pendetide were performed from 1999 to 2004 using two different SPECT/CT scanners, a prototype SPECT/CT system and a commercial SPECT/CT system (Discovery VH, GE Healthcare, Waukesha, WI). SPECT projection data from both systems were reconstructed using an experimental iterative algorithm that compensates for both photon attenuation and collimator blurring. In addition, the data obtained from the commercial system were reconstructed with attenuation correction using an OSEM reconstruction supplied by the camera manufacturer for routine clinical interpretation. For 12 sets of patient data, SPECT images reconstructed using the experimental algorithm were interpreted separately and compared with interpretation of images obtained using the standard reconstruction technique. The experimental reconstruction algorithm improved spatial resolution, reduced streak artifacts, and yielded a better correlation with anatomic details of CT in comparison to conventional reconstruction methods (e.g., filtered back-projection or OSEM with attenuation correction only). Images produced with the experimental algorithm produced a subjective improvement in the confidence of interpretation for 11 of 12 studies. There were also changes in interpretations for 4 of 12 studies although the changes were not sufficient to alter prognosis or the patient treatment plan.

Correction of photon attenuation and collimator response for a body-contouring SPECT/CT imaging system.

UNLABELLED: (111)In-Capromab pendetide imaging is indicated for postprostatectomy patients at risk for residual or recurrent disease. However, this study is complicated by relatively long times for tumor uptake and background washout that require imaging to be performed several days after radiopharmaceutical administration. In addition, (111)In-capromab pendetide demonstrates uptake in normal structures that produce images that are interpreted best using correlation with anatomic imaging. Finally, the visual quality of radionuclide imaging can be improved with corrections for photon attenuation and for the geometric response of the radionuclide collimator. Therefore, we have evaluated the advantages of using a commercially available dual-modality SPECT/CT system. In this article, we evaluate a novel iterative reconstruction algorithm using the SPECT/CT data obtained from phantoms and (111)In-capromab pendetide patient studies. METHODS: Phantom data acquired with the dual-head SPECT camera were reconstructed using both filtered backprojection (FBP) and an iterative maximum-likelihood expectation maximization (MLEM) algorithm incorporating corrections for (a) attenuation coefficient at the effective energy of the radionuclide (either (99m)Tc or (111)In) and (b) collimator response based on experimentally measured depth-dependent spatial resolution of the camera. The collimator response model used the coregistered CT image to estimate the source-target distances produced by the patient-contouring logic of the SPECT camera. Spatial resolution was measured using SPECT images of 2 line sources and uniformity from a uniform cylindric tank. Clinical (111)In-capromab pendetide SPECT/CT data were acquired according to the radiopharmaceutical manufacturer's protocol. Region-of-interest (ROI) analysis of a transverse slice at the level of the sacral base produced mean, median, maximum, and minimum counts per pixel for bone marrow and surrounding soft-tissue ROIs. Ratios of the mean capromab pendetide uptake within marrow to uptake within soft tissue were compared for images reconstructed with FBP versus that obtained from the MLEM method with photon attenuation and collimator response corrections. RESULTS: The source-target distances reconstructed from the patient-specific CT image agreed well with the corresponding values recorded manually from the camera display unit. This information was incorporated into the iterative reconstruction algorithms and improved the quality of SPECT images from phantoms and patients versus SPECT images reconstructed without the depth-dependent collimator response model. Qualitatively, SPECT images reconstructed with corrections for photon attenuation and collimator response showed less background activity and improved target contrast compared with those images reconstructed with FBP. The target-to-background ratio (marrow uptake-to-soft-tissue uptake) was significantly better using MLEM reconstruction than with FBP when mean uptake values were measured. CONCLUSION: A priori anatomic data can be used to enhance the quality of the SPECT image when reconstructed using iterative techniques (e.g., MLEM) that use the CT data to produce a patient-specific attenuation map and a collimator response model based on the body contour produced during the SPECT acquisition.

Calculation and validation of the use of effective attenuation coefficient for attenuation correction in In-111 SPECT.

Nuclear medicine tracers using 111In as a radiolabel are increasing in their use, especially in the domain of oncologic imaging. In these applications, it often is critical to have the capability of quantifying radionuclide uptake and being able to relate it to the biological properties of the tumor. However, images from single photon emission computed tomography (SPECT) can be degraded by photon attenuation, photon scattering, and collimator blurring; without compensation for these effects, image quality can be degraded, and accurate and precise quantification is impossible. Although attenuation correction for SPECT is becoming more common, most implementations can only model single energy radionuclides such as 99mTc and 123I. Thus, attenuation correction for 111In is challenging because it emits two photons (171 and 245 keV) at nearly equal rates (90.2% and 94% emission probabilities). In this paper, we present a method of calculating a single "effective" attenuation coefficient for the dual-energy emissions of 111In, and that can be used to correct for photon attenuation in radionuclide images acquired with this radionuclide. Using this methodology, we can derive an effective linear attenuation coefficient Micro(eff) and an effective photon energy E(eff) based on the emission probabilities and linear attenuation coefficients of the 111In photons. This approach allows us to treat the emissions from 111In as a single photon with an effective energy of 210 keV. We obtained emission projection data from a tank filled with a uniform solution of 111In. The projection data were reconstructed using an iterative maximum-likelihood algorithm with no attenuation correction, and with attenuation correction assuming photon energies of 171, 245, and 210 keV (the derived E(eff)). The reconstructed tomographic images demonstrate that the use of no attenuation correction, or correction assuming photon energies of 171 or 245 keV introduces inaccuracies into the reconstructed radioactivity distribution when compared against the effective energy method. In summary, this work provides both a theoretical framework and experimental methodology of attenuation correction for the dual-energy emissions from 111In. Although these results are specific to 111In, the foundation could easily be extended to other multiple-energy isotopes.

In vitro effect of gonadotropin-releasing hormone agonist on natural killer cell cytolysis in women with and without endometriosis.

OBJECTIVE: The purpose of this study was to assess the in vitro effect of gonadotropin-releasing hormone agonist on natural killer cell activity in women with and without endometriosis and to ascertain whether gonadotropin-releasing hormone agonist effects on natural killer cell activity are direct or mediated solely through the hypoestrogenic state that they produce in vivo. STUDY DESIGN: With use of a chromium 51 release microcytotoxicity assay with K562 target cells, natural killer cell activity was measured after the incubation of mononuclear cells with leuprolide acetate that was obtained from 16 patients with endometriosis and 11 control subjects. RESULTS: The cytotoxicity of natural killer cells that were obtained from patients with endometriosis was reduced significantly (P<.001) with leuprolide. Natural killer cell cytotoxicity from control patients was also significantly decreased (P=.005) with gonadotropin-releasing hormone agonist. Natural killer cell cytotoxicity was significantly lower in patients with endometriosis than in control patients (P=.029). CONCLUSION: These findings suggest a direct immunomodulatory role of gonadotropin-releasing hormone agonist on natural killer cell activity and confirm previous findings that patients with endometriosis have reduced natural killer cell cytotoxicity.