bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare Student Stereotypes: A Systematic Review with Implications for Interprofessional Collaboration
Authors: Cook Karey , Stoecker Judith
Published: March 2018

Background: Stereotyping is one factor theorized to facilitate or inhibit effective interprofessional healthcare education and collaboration. The primary purpose of this paper is to systematically review the literature to determine what stereotypes are present among healthcare students about other healthcare students and practitioners. The secondary purpose of this paper is to identify the instruments most commonly used to measure stereotypes held by healthcare practitioners and students. Methods and Findings: A search of nine electronic databases identified studies that examined stereotypes among healthcare students. Studies were included if they met three search criteria: utilized quantitative methods; collected data on the stereotypes of healthcare students, including medical students, toward other healthcare students or healthcare practitioners; and included participants who were enrolled in a professional healthcare program. Thirteen studies were identified for this review. The results demonstrate that students of various healthcare professions hold stereotypes characterized by both positive and negative adjectives of students and practitioners in their own and other healthcare professions. Conclusions: The presence of stereotypes among students may have an influence on patterns of communication and collaboration during future practice in the healthcare environment. Key Words: Stereotypes, Interprofessional, Healthcare Students, Healthcare Education
Attributes of Effective Interprofessional Placement Facilitation
Authors: Nicol Paul , Forman Dawn
Published: March 2018

Background: The quality of facilitation is an important influence on the efficacy of interprofessional education (IPE) delivery. The research objective was to increase understanding of the attributes of effective facilitation of students during external IPE placements in primary care situations.Methods and Findings: A thematic analysis of the experiences of academics, students, and placement-site staff at three placement sites was employed to explore participants’ perceptions of the attributes of effective IPE facilitators. These attributes included experience in an interprofessional context, together with an understanding of the specific clinical and assessment requirements of different disciplines. Facilitators also needed empathy with respect to the requirements of the external IPE placement sites and the ability to liaise between student and site needs.Conclusions: Models of IPE placement facilitation were most effective when, while following general principles, facilitators tailored them specifically for the individual situations of the placement sites and the learning requirements of particular groups of students. The most rewarding IPE learning experiences occurred when IPE facilitators provided sufficient clinical opportunities for students to work collaboratively with individual clients, provided the students perceived that their participation was relevant to their own discipline.
Measuring Behaviour as Outcome of Interprofessional Interventions: A Review of a Recent Tool Inventory.
Authors: Deutschlander Siegrid , Mallinson Sara
Published: March 2018

Background: This article discusses a recently developed inventory of questionnaires by a former working group of the Canadian Interprofessional Health Collaborative (CIHC) to promote interprofessional (IP) intervention (education and practice) and program evaluation. The classification of questionnaires into six outcome levels revealed an unusually large number focusing on behavioural outcomes. Behavioural outcomes are key measures for evaluating IP interventions, and we decided to further explore the design of questionnaires in this inventory.Methods and Findings: The data presented in this article are based on a systematic search and review of questionnaires published in peer-reviewed journals between 2000 and 2010 that evaluate outcomes related to interprofessional education and collaborative practice. The review was used to construct an inventory that placed questionnaires into six outcome levels: attitudes; knowledge, skills, and abilities; collaborative behaviour of providers at the workplace; collaboration as part of organizational practice; patient satisfaction with collaboration, and provider satisfaction with collaboration. We took a closer look at the subgroup of measures on collaborative behaviour of providers (Level 3 Outcome). We found that the questionnaires included in Level 3 measure a range of competencies. The wording of the subscale items was at times difficult to interpret. While some statements can be clearly attributed to measuring behaviour, others could be seen as measuring some sort of attitudes, beliefs, or knowledge. Since subscale items tended to be a combination of indicators, it was difficult to attribute questionnaires to one particular level.Conclusions: Designing questionnaires for evaluating outcomes from IP interventions is a challenge, especially when behavioural competencies are of interest. We would welcome more attention paid to the input of potential users in questionnaire construction, who are mostly left with little guidance on how to interpret the questions. Triangulation of methods to supplement the current focus on subjective outcome evaluations from IP interventions would also enhance this research.
Comparison of Communications Styles Amongst Students in Allied Health Professions Programs: How Do Our Students Communicate with Other Healthcare Providers?
Authors: Buhler Amber Virya King , Coplen Amy E , Davis Shawn , Nijjar Bobby
Published: March 2018

Background: Optimal patient outcomes require communication between providers in multiple professions to initiate referrals, communicate patient treatment, and coordinate care. While there is a clear need for increased understanding of the terminology, skills, and scopes of practice of professional colleagues, these tools are of limited effectiveness if there is poor interpersonal communication between team members. Multiple bodies for Interprofessional Practice and Education (IPP/IPE) identify communication skills as an integral part of education. In fact, the third competency domain set down by the Interprofessional Education Collaborative, Interprofessional Communication, states that professionals should, “Recognize how one’s own uniqueness, including experience level, expertise, culture, power, and hierarchy within the healthcare team, contributes to effective communication, conflict resolution, and positive interprofessional working relationships” [1].Methods and Findings: As part of a required interprofessional competence course, first-year students in ten health professions programs completed the Personal Coaching Style Inventory (PSCI) to self-identify personal communication styles. A series of one-way analysis of variance (ANOVA) analyses followed by Tukey post-hoc analyses were performed in order to identify significant differences in PSCI component scores between programs. Within groups, students discussed personal and cohort-wide findings as they impact teamwork. The majority of students identified with the Mediator style. Differences in style were also found in relation to profession, gender, and race. The activity prompted discussion of varied roles in team dynamics, and how differences in style could affect interprofessional teamwork.Conclusions: Self-awareness of personal communication styles as well as predominant styles of other health professions may enhance interprofessional communication\skills. The skill with which students approach their team roles in heterogeneous groups following graduation has the potential to increase team functionality and patient outcomes.
Factors Affecting Interprofessional Collaboration when Communicating through the use of Information and Communication Technologies: A Literature Review
Authors: Graves Monica , Doucet Dr. Shelley
Published: March 2018

Abstract Background Information and communication technologies (ICTs) are increasingly being used internationally as a cost-effective and efficient way to provide care for patients in rural and remote settings, often referred to as telemedicine. There have been various studies that have examined the effectiveness of telemedicine implementation on patient outcomes, and the factors that enable successful telemedicine program implementation. The purpose of this narrative literature review was to explore a different side of the issue, with the objective to examine the factors that affect interprofessional collaboration when communicating through the use of ICTs in telemedicine settings.   Methods and Findings A total of 56 papers were included in this review. Using a narrative review design, analysis of the papers revealed several factors that act as facilitators and barriers to interprofessional collaboration when communicating through the use of ICTs. Facilitators included training and planning; ICT system supports; establishing good rapport and communication patterns; patient-centredness; willingness to adapt to and accept the technology; and key individuals providing leadership and administrative support. Barriers included technical issues; coordination and organizational challenges; and problematic relationships.   Conclusions From the facilitators and barriers, recommendations have been compiled for stakeholders involved in telemedicine initiatives to consider on how to support interprofessional collaboration in telemedicine.
Independence, size and performance of the board: An emerging market research
Authors: Tulung Joy Elly , Ramdani Dendi
Published: March 2018

The purpose of this article is to find the link between board independence, board size and BPD (regional development bank) performance for describing the corporate governance in regional development bank. The sample of firms consists all 26’s BPD in Indonesia in the period 2010-2014; we take secondary data from the annual report of each BPD, total 203 top executives who are members of the boards of all BPD in Indonesia. The results are the influence of the board independence and board size on the BPD performance. The sample employed all the members of the boards of BPD in Indonesia giving us a confidence in generalization our findings. The statistical method used to test the hypotheses is OLS regression. This method was applied to measure the relationship between board independence, board size and BPD performance. The results suggested that there is a positive relationship between board independence, board size and BPD performance
Pozycja konkurencyjna banków spółdzielczych w segmencie mikroprzedsiębiorstw
Authors: Idzik Marcin
Published: March 2018

Celem opracowania była ocena pozycji konkurencyjnej banków spółdzielczych oraz ich zdolności do kreowania tendencji rozwojowych i skutecznego pozyskiwania nowych klientów w segmencie mikroprzedsiębiorstw. Źródło danych empirycznych stanowiły wyniki ogólnopolskich badań zrealizowanych na reprezentatywnej próbie N = 800 przedsiębiorstw o zatrudnieniu do 10 pracowników oraz rocznych obrotach do 2 mln euro. Analiza objęto udziały rynkowe, znajomość, potencjał i wizerunku marki oraz satysfakcję klientów. Banki spółdzielcze nie wykorzystują w pełni swoich walorów w budowaniu przewagi konkurencyjnej. Wysokie udziały rynkowe zawdzięczają stabilnej bazie „starych” klientów. Banki spółdzielcze nie są preferowane przez potencjalnych klientów. Pozycja konkurencyjna wynika z niszowych obszarów, w których działają banki spółdzielcze, kosztów obsługi oraz emocjonalnych uwarunkowań działania na lokalnym rynku. Stosowanie narzędzi marketingowych jest nieuniknione i powinno stać się elementarną częścią wspomagania funkcjonowania banków spółdzielczych.
Rozmiary i regionalne zróżnicowanie polskiego rynku nieruchomości rolnych
Authors: Klusek Tomasz
Published: March 2018

Rynek nieruchomości nie jest rynkiem jednolitym, w związku z tym, w zależności od przyjętych kryteriów, można dokonać jego podziału na różne segment. Do najczęściej stosowanych kryteriów klasyfikacji tego rynku, dla potrzeb prowadzonych analiz, zaliczyć należy kryterium przedmiotowe. Uwzględnia ono funkcje pełnione przez nieruchomości, a jednym z segmentów wyodrębnianych na jego podstawie jest rynek nieruchomości rolnych. Dane dotyczące obrotu nieruchomościami rolnymi w skali kraju i poszczególnych województw mogą być wykorzystane dla różnych celów, w szczególności dla potrzeb wyznaczania kierunków przekształceń strukturalnych w rolnictwie. W tym kontekście istotne jest poznanie uwarunkowań tego zjawiska, jego natężenia oraz struktury, co jest przedmiotem niniejszego opracowania.
The power of restorative apologies (real and imagined) for victims and offenders
Authors: Walker Lorenn , Tarutani Cheri , Furman Ben
Published: March 2018

Shame can be felt after causing harm and after being harmed by wrongdoing.
Failure to address shame can increase the possibility of the victim-offender
overlap, making victims more likely to offend and offenders more likely to be
victimized. An online, individually applied, restorative apology process
could help prevent the victim-offender overlap by helping heal harm. People
who have caused harm are given the opportunity to be accountable and explore
how they might help repair damage they have caused, while those harmed can
address any violation and shame felt. Anecdotal evidence indicates
restorative apologies delivered either personally, or only imagined, can help
individuals heal from harm and trauma. Open access to restorative apology
processes is provided at www.apologyletter.org. The purpose of this paper is
to show how the confidential apology program can help people address harm and
shame. Appendices A and B provide an imagined apology exercise and guidelines
for preparing a combined apology and gratitude letter, which can assist
individuals affected by wrongdoing.
Aortic coarctation and associated cardiac lesions-optimal therapeutic approach: Report of 2 cases
Authors: Velinovic Milos , Karan Radmila , Kovacevic-Kostic Natasa , Obrenovic-Kircanski Biljana , Stojimirov Milica , Milicevic Vlado , Nikolic Dejan , Milic Dragan
Published: March 2018

Abstract Introduction. Aortic coarcation is a congenital condition mostly detected and treated during childhood. Adult patients with coarctation and associated cardiac lesions represent a challenge and a subject of debates concerning adequate treatment. We report 2 patients with aortic coartation when a surgical treatment was necessary. Case report. First patient was a 61-year-old male with previous mechanical aortic valve implantation. He underwent one stage surgical reconstruction of aortic coarctation and surgical repair of aneurysm of ascending aorta. The second patient was a 49- year-old female with aortic aneurysm, bicuspid aortic valve, severe aortic insufficiency and coarctation of aorta below branching of subclavian artery. She underwent the Bentall procedure and surgical repair of coarctation by bypass where the proximal anastomosis was made between the terminal part of Dacron graft and the lateral part of graft used for Bentall, while the distal anastomosis was made between the terminal part of Dacron graft and the lateral part of descending aorta below coarctation. The postoperative course and the follow-up of the patients of 3 and 1 year, respectively, were without complications. Conclusion. Single operation is a better choice in the patients with concomitant pathology such as the aortic aneurysm, or aortic valve disease. Each patient should be analyzed on a single basis, and a decision about a surgical technique and surgical course brought accordingly.
Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach
Authors: Johnson Mai , Sato Makoto , Burton Jeremy , Gambhir Sanjiv S. , Carey Michael , Wu Lily
Published: March 2018

Cancer gene therapy based on tissue-restricted expression of cytotoxic gene should achieve superior therapeutic index over an unrestricted method. This study compared the therapeutic effects of a highly augmented, prostate-specific gene expression method to a strong constitutive promoter-driven approach. Molecular imaging was coupled to gene therapy to ascertain real-time therapeutic activity. The imaging reporter gene (luciferase) and the cytotoxic gene (herpes simplex thymidine kinase) were delivered by adenoviral vectors injected directly into human prostate tumors grafted in SCID mice. Serial bioluminescence imaging, positron emission tomography, and computed tomography revealed restriction of gene expression to the tumors when prostate-specific vector was employed. In contrast, administration of constitutive active vector resulted in strong signals in the liver. Liver serology, tissue histology, and frail condition of animals confirmed liver toxicity suffered by the constitutive active cohorts, whereas the prostate-targeted group was unaffected. The extent of tumor killing was analyzed by apoptotic staining and human prostate marker (prostate-specific antigen). Overall, the augmented prostate-specific expression system was superior to the constitutive approach in safeguarding against systemic toxicity, while achieving effective tumor killing. Integrating noninvasive imaging into cytotoxic gene therapy will provide a useful strategy to monitor gene expression and therapeutic efficacy in future clinical protocols.
In Vivo Testing of Renilla Luciferase Substrate Analogs in an Orthotopic Murine Model of Human Glioblastoma
Authors: Otto-Duessel Maya , Khankaldyyan Vazgen , Gonzalez-Gomez Ignacio , Jensen Michael C. , Laug Walter E. , Rosol Michael
Published: March 2018

In vivo bioluminescent imaging using cells expressing Renilla luciferase is becoming increasingly common. Hindrances to the more widespread use of Renilla luciferase are the high autoluminescence of its natural substrate, coelenterazine, in plasma; the relatively high absorbance by tissue of the light emitted by the enzyme–substrate reaction; rapid clearance of the substrate; and significant cost. These factors, save for the cost, which has its own limiting effect on use, can combine to reduce the sensitivity of in vivo assays utilizing this reporter system, and methods of increasing light output or decreasing autoluminescence could be of great benefit. A number of analogs of coelenterazine are being investigated that may accomplish one or both of these goals. In this study, we report on the testing of two new substrate analogs, EnduRen™ and ViviRen™, manufactured by Promega Corporation, in an orthotopic murine model of human glioblastoma expressing Renilla luciferase. We have tested these analogs in this cell line, both in vitro and in vivo, and find that the substrate ViviRen results in significantly greater light output than the natural substrate or the other analog EnduRen. This new substrate could be valuable for studies where greater sensitivity is important.
Bioluminescent Monitoring of NIS-Mediated 131I Ablative Effects in MCF-7 Xenografts
Authors: Ghosh Malavika , Gambhir Sanjiv Sam , De Abhijit , Nowels Kent , Goris Michael , Wapnir Irene
Published: March 2018

Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with 131I is predicated on the expression of the Na+/I− symporter (NIS) in many tumors and uptake of I in some. The pattern of 131I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of 131I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in 131I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in 131I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less 99mTcO4 than untreated tumors. NIS immunoreactivity was present in <50% of 131I-treated cells compared to 85–90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after 131I administration was observed in NIS-expressing breast cancer xenografts.
Optical Imaging of Cellular Immunotherapy against Prostate Cancer
Authors: Tavri Sidhartha , Jha Priyanka , Meier Reinhard , Henning Tobias D. , Müller Tina , Hostetter Daniel , Knopp Christiane , Johansson Magnus , Reinhart Verena , Boddington Sophie , Sista Akhilesh , Wels Winfried S. , Daldrup-Link Heike E.
Published: March 2018

The purpose of this study was to track fluorophore-labeled, tumor-targeted natural killer (NK) cells to human prostate cancer xenografts with optical imaging (OI). NK-92-scFv(MOC31)-zeta cells targeted to the epithelial cell adhesion molecule (EpCAM) antigen on prostate cancer cells and nontargeted NK-92 parental cells were labeled with the near-infrared dye DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). The fluorescence, viability, and cytotoxicity of the labeled cells were evaluated. Subsequently, 12 athymic rats with prostate cancer xenografts underwent OI scans before and up to 24 hours postinjection of DiD-labeled parental NK-92 cells or NK-92-scFv(MOC31)-zeta cells. The tumor fluorescence intensity was measured and compared between pre- and postinjection scans and between both groups using t-tests. OI data were confirmed with fluorescence microscopy. In vitro studies demonstrated a significant increase in the fluorescence of labeled cells compared with unlabeled controls, which persisted over a period of 24 hours without any significant change in the viability. In vivo studies demonstrated a significant increase in tumor fluorescence at 24 hours postinjection of tumor-targeted NK-92-scFv(MOC31)-zeta cells but not parental NK cells. Ex vivo OI scans and fluorescence microscopy confirmed a specific accumulation of NK-92-scFv(MOC31)-zeta cells but not parental NK cells in the tumors. Tumor-targeted NK-92-scFv(MOC31)-zeta cells could be tracked to prostate cancer xenografts with OI.
Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies
Authors: Streeter Jason E. , Gessner Ryan , Miles Iman , Dayton Paul A.
Published: March 2018

Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvß3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging.
Integrated Imaging Approach to Tumor Model Mice Using Bioluminescence Imaging and Magnetic Resonance Imaging
Authors: Inoue Yusuke , Masutani Yoshitaka , Kiryu Shigeru , Haishi Tomoyuki , Watanabe Makoto , Tojo Arinobu , Ohtomo Kuni
Published: March 2018

We developed an integrated imaging method using bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) and applied it to mouse tumor monitoring. BLIs and MRIs were successively acquired from mice fixed on a transparent flat plate and were registered using three small markers. After spatial coregistration, the two-dimensional BLI was fused with all MRI slices. The accuracy of image registration was evaluated using fluorescence imaging and MRI of many markers attached to the mice. Mice were inoculated with luciferase-expressing tumor cells subcutaneously or directly into the liver, and disease progression was evaluated repeatedly by integrated BLI-MRI. Image registration was achieved with acceptable accuracy, although the registration error increased with increasing distance from the center of the imaging field and was larger in imaging the convex dorsal side of the mouse than in imaging the flat ventral side. Integrated BLI-MRI allowed longitudinal assessment of disease progression and appeared to facilitate detailed interpretation of the imaging findings. It aided the anatomic localization of lesions demonstrated by BLI and recognition of MRI abnormalities corresponding to BLI foci. Integrated BLI-MRI is feasible and appears to be a practical method for comprehensive, longitudinal assessment of disease model mice.
Hisstology: High Spectral and Spatial Resolution Magnetic Resonance Imaging Detection of Vasculature Validated by Histology and Micro–Computed Tomography
Authors: Haney Chad R. , Pelizzari Charles A. , Foxley Sean , Zamora Marta A. , Mustafi Devkumar , Tretiakova Maria , Li Shihong , Fan Xiaobing , Karczmar Gregory S.
Published: March 2018

High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging (EPSI), can be used to acquire water spectra from each small image voxel. These images are sensitive to changes in local susceptibility caused by superparamagnetic iron oxide particles (SPIO); therefore, we hypothesized that images derived from HiSS data are very sensitive to tumor neovasculature following injection of SPIO. Accurate image registration was used to validate HiSS detection of neovasculature with histology and micro–computed tomographic (microCT) angiography. Athymic nude mice and Copenhagen rats were inoculated with Dunning AT6.1 prostate tumor cells in the right hind limb. The tumor region was imaged pre– and post–intravenous injection of SPIO. Three-dimensional assemblies of the CD31-stained histologic slices of the mouse legs and the microCT images of the rat vascular casts were registered with EPSI. The average distance between HiSS-predicted regions of high vascular density on magnetic resonance imaging and CD31-stained regions on histology was 200 μm. Similarly, vessels identified by HiSS in the rat images coincided with vasculature in the registered microCT image. The data demonstrate a strong correlation between tumor vasculature identified using HiSS and two gold standards: histology and microCT angiography.
Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy
Authors: Luboldt Wolfgang , Hartmann Holger , Wiedemann Bärbel , Zöphel Klaus , Luboldt Hans-Joachim
Published: March 2018

The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI]) were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]). The SUVmaxof the normal liver was below 10 (7.2 ± 1.3) in all patients and without significant changes. Overall therapy changes (Δ) per patient (mean [95% CI]) were statistically significant with p < .01 for ΔCgA = −43 (−69 to −17), ΔSUVmax = −22 (−29 to −14), and ΔVOI10SUV = −53 (−68 to −38)% and significant with p < .05 for ΔVOIliver+10% = −29 (−55 to −3)%, ΔVOIliver+20% = −32 (−62 to −2) and ΔVOIliver+30% = −37 (−66 to −8). Correlations were found only between ΔCgA and ΔVOI10SUV ( r = .595; p < .01), ΔSUVmax and ΔVOI10SUV (0.629, p < .01), and SUVmax and ΔSUVmax ( r = .446; p < .05). 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended).
Magnetic Resonance Cell-Tracking Studies: Spectrophotometry-Based Method for the Quantification of Cellular Iron Content after Loading with Superparamagnetic Iron Oxide Nanoparticles
Authors: Böhm Ingrid
Published: March 2018

The purpose of this article is to present a user-friendly tool for quantifying the iron content of superparamagnetic labeled cells before cell tracking by magnetic resonance imaging (MRI). Iron quantification was evaluated by using Prussian blue staining and spectrophotometry. White blood cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Labeling was confirmed by light microscopy. Subsequently, the cells were embedded in a phantom and scanned on a 3 T magnetic resonance tomography (MRT) whole-body system. Mean peak wavelengths Λpeak was determined at A720nm (range 719–722 nm). Linearity was proven for the measuring range 0.5 to 10 μg Fe/mL ( r = .9958; p = 2.2 × 10−12). The limit of detection was 0.01 μg Fe/mL (0.1785 mM), and the limit of quantification was 0.04 μg Fe/mL (0.714 mM). Accuracy was demonstrated by comparison with atomic absorption spectrometry. Precision and robustness were also proven. On T2-weighted images, signal intensity varied according to the iron concentration of SPIO-labeled cells. Absorption spectrophotometry is both a highly sensitive and user-friendly technique that is feasible for quantifying the iron content of magnetically labeled cells. The presented data suggest that spectrophotometry is a promising tool for promoting the implementation of magnetic resonance-based cell tracking in routine clinical applications (from bench to bedside).
Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging of Neuroinflammation in a Rat Model of Radicular Pain
Authors: Thorek Daniel L.J. , Weisshaar Christine L. , Czupryna Julie C. , Winkelstein Beth A. , Tsourkas Andrew
Published: March 2018

In many clinical cases of radicular pain, no noticeable neuropathology is detected by conventional medical imaging strategies. Superparamagnetic iron oxide (SPIO) nanoparticles were evaluated as magnetic resonance contrast agents to specifically detect neuroinflammation at sites of painful injury in a rat model of cervical nerve root compression. Two separate groups of rats were used: an injury group that underwent controlled transient compression of the dorsal root and a sham group that received the same surgical procedures but no injury. Precontrast magnetic resonance imaging (MRI) was performed 6 days after surgery, followed by administration of SPIO via tail vein injection. After 24 hours, T2*-weighted imaging at the site of root injury revealed a postcontrast enhancement of 72.9 ± 31%. This was significantly greater than that of injured animals prior to SPIO administration (5.3 ± 12.9%). SPIO did not generate any significant postcontrast enhancement in the nerve roots of the sham group. Histology confirmed colocalization of SPIO with macrophage at the injury site. These findings suggest that SPIO-enhanced MRI may be a valuable tool to identify otherwise undetectable nerve root compression and enable improved patient management.
Intraoperative Imaging of Positron Emission Tomographic Radiotracers Using Cerenkov Luminescence Emissions
Authors: Holland Jason P. , Normand Guillaume , Ruggiero Alessandro , Lewis Jason S. , Grimm Jan
Published: March 2018

Imaging the location and extent of cancer provides invaluable information before, during, and after surgery. The majority of “image-guided” methods that use, for example, positron emission tomography (PET) involve preoperative imaging and do not provide real-time information during surgery. It is now well established that the inherent optical emissions (Cerenkov radiation) from various β-emitting radionuclides can be visualized by Cerenkov luminescence imaging (CLI). Here we report the full characterization of CLI using the positron-emitting radiotracer 89Zr-DFO-trastuzumab for target-specific, quantitative imaging of HER2/neu-positive tumors in vivo. We also provide the first demonstration of the feasibility of using CLI for true image-guided, intraoperative surgical resection of tumors. Analysis of optical CLIs provided accurate, quantitative information on radiotracer biodistribution and tissue uptake that correlated well with the concordant PET images. CLI, PET, and biodistribution studies revealed target-specific uptake of 89Zr-DFO-trastuzumab in BT-474 ( HER2/neu positive) versus MDA-MB-468 ( HER2/neu negative) xenografts in the same mice. Competitive inhibition (blocking) studies followed by CLI also confirmed the in vivo immunoreactivity and specificity of 89Zr-DFO-trastuzumab for HER2/neu. Overall, these results strongly support the continued development of CLI as a preclinical and possible clinical tool for use in molecular imaging and surgical procedures for accurately defining tumor margins.
High-Resolution Computed Tomography of Single Breast Cancer Microcalcifications in Vivo
Authors: Inoue Kazumasa , Liu Fangbing , Hoppin Jack , Lunsford Elaine P. , Lackas Christian , Hesterman Jacob , Lenkinski Robert E. , Fujii Hirofumi , Frangioni John V.
Published: March 2018

Microcalcification is a hallmark of breast cancer and a key diagnostic feature for mammography. We recently described the first robust animal model of breast cancer microcalcification. In this study, we hypothesized that high-resolution computed tomography (CT) could potentially detect the genesis of a single microcalcification in vivo and quantify its growth over time. Using a commercial CT scanner, we systematically optimized acquisition and reconstruction parameters. Two ray-tracing image reconstruction algorithms were tested: a voxel-driven “fast” cone beam algorithm (FCBA) and a detector-driven “exact” cone beam algorithm (ECBA). By optimizing acquisition and reconstruction parameters, we were able to achieve a resolution of 104 μm full width at half-maximum (FWHM). At an optimal detector sampling frequency, the ECBA provided a 28 μm (21%) FWHM improvement in resolution over the FCBA. In vitro, we were able to image a single 300 μm X 100 μm hydroxyapatite crystal. In a syngeneic rat model of breast cancer, we were able to detect the genesis of a single microcalcification in vivo and follow its growth longitudinally over weeks. Taken together, this study provides an in vivo “gold standard” for the development of calcification-specific contrast agents and a model system for studying the mechanism of breast cancer microcalcification.
Rh-I-UEA-1 Polymerized Liposomes Target and Image Adenomatous Polyps in the APCMin/+ Mouse Using Optical Colonography
Authors: Roney Celeste A. , Xu Biying , Xie Jianwu , Yuan Shuai , Wierwille Jeremiah , Chen Chao-Wei , Chen Yu , Griffiths Gary L. , Summers Ronald M.
Published: March 2018

Mutated adenomatous polyposis coli ( APC) genes predispose transformations to neoplasia, progressing to colorectal carcinoma. Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents were fabricated to locate and image adenomatous polyps in APC Min/+ mice. The biomarker α-l-fucose covalently joins the liposomal conjugated lectin Ulex europaeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (rhodamine B 532 nm emission, 590–620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4-fold labeling efficiency. High-resolution coregistered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal the spatial correlation of contrast distribution and tissue morphology. Freshly excised APC Min bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or iohexol (Omnipaque) and imaged by the three techniques. Computed tomographic quantitative analyses did not confirm that targeted liposomes more strongly bound polyps than nontargeted liposomes or iohexol (Omnipaque) alone. OCT, with anatomic depth capabilities, along with the coregistered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes α-l-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APC Min mice.
Positron Emission Tomographic Imaging of the Cannabinoid Type 1 Receptor System with [11C]OMAR ([11C]JHU75528): Improvements in Image Quantification Using Wild-Type and Knockout Mice
Authors: Herance Raúl , Rojas Santiago , Abad Sergio , Jiménez Xavier , Gispert Juan Domingo , Millán Olga , Martín-García Elena , Burokas Aurelijus , Serra Miquel Àngel , Maldonado Rafael , Pareto Deborah
Published: March 2018

In this study, we assessed the feasibility of using positron emission tomography (PET) and the tracer [11C]OMAR ([11C]JHU75528), an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1) receptor system. Wild-type (WT) andCB1 knockout (KO) animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50%) than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [11C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.
Detection of Myocardial Ischemia-Reperfusion Injury Using a Fluorescent Near-Infrared Zinc(II)-Dipicolylamine Probe and 99mTc Glucarate
Authors: wyffels Leonie , Gray Brian D. , Barber Christy , Pak Koon Y. , Forbes Safiyyah , Mattis Jeffrey A. , Woolfenden James M. , Liu Zhonglin
Published: March 2018

A fluorescent zinc 2,2′-dipicolylamine coordination complex PSVue®794 (probe 1) is known to selectively bind to phosphatidylserine exposed on the surface of apoptotic and necrotic cells. In this study, we investigated the cell death targeting properties of probe 1 in myocardial ischemia-reperfusion injury. A rat heart model of ischemia-reperfusion was used. Probe 1, control dye, or 99mTc glucarate was intravenously injected in rats subjected to 30-minute and 5-minute myocardial ischemia followed by 2-hour reperfusion. At 90 minutes or 20 hours postinjection, myocardial uptake was evaluated ex vivo by fluorescence imaging and autoradiography. Hematoxylin-eosin and cleaved caspase-3 staining was performed on myocardial sections to demonstrate the presence of ischemia-reperfusion injury and apoptosis. Selective accumulation of probe 1 could be detected in the area at risk up to 20 hours postinjection. Similar topography and extent of uptake of probe 1 and 99mTc glucarate were observed at 90 minutes postinjection. Histologic analysis demonstrated the presence of necrosis, but only a few apoptotic cells could be detected. Probe 1 selectively accumulates in myocardial ischemia-reperfusion injury and is a promising cell death imaging tool.
Temporal Changes in Phosphatidylserine Expression and Glucose Metabolism after Myocardial Infarction: An in Vivo Imaging Study in Mice
Authors: Lehner Sebastian , Todica Andrei , Brunner Stefan , Uebleis Christopher , Wang Hao , Wängler Carmen , Herbach Nadja , Herrler Tanja , Böning Guido , Laubender Rüdiger Paul , Cumming Paul , Schirrmacher Ralf , Franz Wolfgang , Hacker Marcus
Published: March 2018

Positron emission tomography (PET) for in vivo monitoring of phosphatidylserine externalization and glucose metabolism can potentially provide early predictors of outcome of cardioprotective therapies after myocardial infarction. We performed serial [68Ga]annexin A5 PET (annexin-PET) and [18F]fluorodeoxyglucose PET (FDG-PET) after myocardial infarction to determine the time of peak phosphatidylserine externalization in relation to impaired glucose metabolism in infracted tissue. Annexin- and FDG-PET recordings were obtained in female (C57BL6/N) mice on days 1 to 4 after ligation of the left anterior descending (LAD) artery. [68Ga]annexin A5 uptake (%ID/g) in the LAD artery territory increased from 1.7 ± 1.1 on day 1 to 5.0 ± 3.3 on day 2 and then declined to 2.0 ± 1.4 on day 3 (p = .047 vs day 2) and 1.6 ± 1.4 on day 4 ( p = .014 vs day 2). These results matched apoptosis rates as estimated by autoradiography and fluorescein staining. FDG uptake (%ID/g) declined from 28 ± 14 on day 1 to 14 ± 3.5 on day 4 ( p < .0001 vs day 1). Whereas FDG-PET revealed continuous loss of cell viability after permanent LAD artery occlusion, annexin-PET indicated peak phosphatidylserine expression at day 2, which might be the optimal time point for therapy monitoring.
Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform
Authors: Lee Sanghyeb , Gregor Jens , Osborne Dustin
Published: March 2018

This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.
Ultrasound Backscatter Microscopy Image-Guided Intraventricular Gene Delivery at Murine Embryonic Age 9.5 and 10.5 Produces Distinct Transgene Expression Patterns at the Adult Stage
Authors: Jang Jiwon , Ahn Jyhyun , Lee Nayeon , Kim Seong-Tae , Kweon Dae-Hyuk , Cho Jae Youl , Park Kye Won , Kim Sunyoung , Yoon Keejung
Published: March 2018

In utero injection of a retroviral vector into the embryonic telencephalon aided by ultrasound backscatter microscopy permits introduction of a gene of interest at an early stage of development. In this study, we compared the tissue distribution of gene expression in adult mice injected with retroviral vectors at different embryonic ages in utero. Following ultrasound image-guided gene delivery (UIGD) into the embryonic telencephalon, adult mice were subjected to whole-body luciferase imaging and immunohistochemical analysis at 6 weeks and 1 year postinjection. Luciferase activity was observed in a wide range of tissues in animals injected at embryonic age 9.5 (E9.5), whereas animals injected at E10.5 showed brain-localized reporter gene expression. These results suggest that mouse embryonic brain creates a closed and impermeable structure around E10. Therefore, by injecting a transgene before or after E10, transgene expression can be manipulated to be local or systemic. Our results also provide information that widens the applicability of UIGD beyond neuroscience studies.
Translocator Protein (18 kDa) Mapping with [125I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death
Authors: Arlicot Nicolas , Tronel Claire , Bodard Sylvie , Garreau Lucette , de la Crompe Brice , Vandevelde Inge , Guilloteau Denis , Antier Daniel , Chalon Sylvie
Published: March 2018

Excitotoxicity leads to an inflammatory reaction involving an overexpression of: translocator protein 18 kDa (TSPO) in cerebral microglia and astrocytes. Therefore, we performed ex vivo explorations with [125]-CLINDE, a TSPO-specific radioligand, to follow the time course of TSPO expression, in parallel with lesion progression, over 90 days after induction of cerebral excitotoxicity in rats intrastriatally injected with quinolinic acid. Biodistribution data showed a significant increase in CLINDE uptake on the injured side from 1 days postlesion (dpl); the maximal striatal binding values evidenced a plateau between 7 and 30 dpl. [125I]-CLINDE binding was displaced from the lesion by PK11195, suggesting TSPO specificity. These results were confirmed by ex vivo autoradiography. Combined immunohistochemical studies showed a marked increase in microglial expression in the lesion, peaking at 14 dpl, and astrocytic reactivity enhanced at 7 and 14 dpl, whereas a prominent neuronal cell loss was observed. At 90 dpl, CLINDE binding and immunoreactivity targeting activated microglia, astrogliosis, and neuronal cell density returned to a basal level. These results show that both neuroinflammation and neuronal loss profiles occurred concomitantly and appeared to be transitory processes. These findings provide the possibility of a therapeutic temporal window to compare the differential effects of antiinflammatory treatments in slowing down neurodegeneration in this rodent model, with potential applications to humans.
Use of a Ray-Based Reconstruction Algorithm to Accurately Quantify Preclinical MicroSPECT Images
Authors: Vandeghinste Bert , Van Holen Roel , Vanhove Christian , De Vos Filip , Vandenberghe Stefaan , Staelens Steven
Published: March 2018

This work aimed to measure the in vivo quantification errors obtained when ray-based iterative reconstruction is used in micro-single-photon emission computed tomography (SPECT). This was investigated with an extensive phantom-based evaluation and two typical in vivo studies using 99mTc and 111In, measured on a commercially available cadmium zinc telluride (CZT)-based small-animal scanner. Iterative reconstruction was implemented on the GPU using ray tracing, including (1) scatter correction, (2) computed tomography-based attenuation correction, (3) resolution recovery, and (4) edge-preserving smoothing. It was validated using a National Electrical Manufacturers Association (NEMA) phantom. The in vivo quantification error was determined for two radiotracers: [99mTc]DMSA in naive mice ( n = 10 kidneys) and [111In]octreotide in mice ( n = 6) inoculated with a xenograft neuroendocrine tumor (NCI-H727). The measured energy resolution is 5.3% for 140.51 keV (99mTc), 4.8% for 171.30 keV, and 3.3% for 245.39 keV (111In). For 99mTc, an uncorrected quantification error of 28 ± 3% is reduced to 8 ± 3%. For 111In, the error reduces from 26 ± 14% to 6 ± 22%. The in vivo error obtained with “mTc-dimercaptosuccinic acid ([99mTc]DMSA) is reduced from 16.2 ± 2.8% to −0.3 ± 2.1% and from 16.7 ± 10.1% to 2.2 ± 10.6% with [111In]octreotide. Absolute quantitative in vivo SPECT is possible without explicit system matrix measurements. An absolute in vivo quantification error smaller than 5% was achieved and exemplified for both [”mTc]DMSA and [111In]octreotide.