A Multimodality Myocardial Perfusion Phantom:Initial Quantitative Imaging Results

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential

A Multimodality Myocardial Perfusion Phantom:Initial Quantitative Imaging Results

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential.</p

Development of a dynamic myocardial perfusion phantom model for tracer kinetic measurements

BACKGROUND: Absolute myocardial perfusion imaging (MPI) is beneficial in the diagnosis and prognosis of patients with suspected or known coronary artery disease. However, validation and standardization of perfusion estimates across centers is needed to ensure safe and adequate integration into the clinical workflow. Physical myocardial perfusion models can contribute to this clinical need as these can provide ground-truth validation of perfusion estimates in a simplified, though controlled setup. This work presents the design and realization of such a myocardial perfusion phantom and highlights initial performance testing of the overall phantom setup using dynamic single photon emission computed tomography. RESULTS: Due to anatomical and (patho-)physiological representation in the 3D printed myocardial perfusion phantom, we were able to acquire 22 dynamic MPI datasets in which 99mTc-labelled tracer kinetics was measured and analyzed using clinical MPI software. After phantom setup optimization, time activity curve analysis was executed for measurements with normal myocardial perfusion settings (1.5 mL/g/min) and with settings containing a regional or global perfusion deficit (0.8 mL/g/min). In these measurements, a specific amount of activated carbon was used to adsorb radiotracer in the simulated myocardial tissue. Such mimicking of myocardial tracer uptake and retention over time satisfactorily matched patient tracer kinetics. For normal perfusion levels, the absolute mean error between computed myocardial blood flow and ground-truth flow settings ranged between 0.1 and 0.4 mL/g/min. CONCLUSION: The presented myocardial perfusion phantom is a first step toward ground-truth validation of multimodal, absolute MPI applications in the clinical setting. Its dedicated and 3D printed design enables tracer kinetic measurement, including time activity curve and potentially compartmental myocardial blood flow analysis

Development of a dedicated 3D printed myocardial perfusion phantom:proof-of-concept in dynamic SPECT

We aim to facilitate phantom-based (ground truth) evaluation of dynamic, quantitative myocardial perfusion imaging (MPI) applications. Current MPI phantoms are static representations or lack clinical hard- and software evaluation capabilities. This proof-of-concept study demonstrates the design, realisation and testing of a dedicated cardiac flow phantom. The 3D printed phantom mimics flow through a left ventricular cavity (LVC) and three myocardial segments. In the accompanying fluid circuit, tap water is pumped through the LVC and thereafter partially directed to the segments using adjustable resistances. Regulation hereof mimics perfusion deficit, whereby flow sensors serve as reference standard. Seven phantom measurements were performed while varying injected activity of 99mTc-tetrofosmin (330–550 MBq), cardiac output (1.5–3.0 L/min) and myocardial segmental flows (50–150 mL/min). Image data from dynamic single photon emission computed tomography was analysed with clinical software. Derived time activity curves were reproducible, showing logical trends regarding selected input variables. A promising correlation was found between software computed myocardial flows and its reference (ρ= − 0.98; p = 0.003). This proof-of-concept paper demonstrates we have successfully measured first-pass LV flow and myocardial perfusion in SPECT-MPI using a novel, dedicated, myocardial perfusion phantom. Graphical abstract: This proof-of-concept study focuses on the development of a novel, dedicated myocardial perfusion phantom, ultimately aiming to contribute to the evaluation of quantitative myocardial perfusion imaging applications. [Figure not available: see fulltext.

Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.

Funder: IBERS, Aberystwyth University PhD studentshipFunder: Higher Education Funding Council for Wales (HEFCW) - Global Challenges Research FundExtracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships

Study protocol: Population screening for colorectal cancer by colonoscopy or CT colonography: A randomized controlled trial

Background: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.Methods and design: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After provid

Special considerations for studies of extracellular vesicles from parasitic helminths: A community‐led roadmap to increase rigour and reproducibility

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved

Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.</p> <p>Methods and design</p> <p>7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.</p> <p>Discussion</p> <p>This study will provide further evidence to enable decision making in population screening for colorectal cancer.</p> <p>Trial registration</p> <p>Dutch trial register: NTR1829</p