Quantitative imaging:systematic review of perfusion/flow phantoms

Background: We aimed at reviewing design and realisation of perfusion/flow phantoms for validating quantitative perfusion imaging (PI) applications to encourage best practices. Methods: A systematic search was performed on the Scopus database for “perfusion”, “flow”, and “phantom”, limited to articles written in English published between January 1999 and December 2018. Information on phantom design, used PI and phantom applications was extracted. Results: Of 463 retrieved articles, 397 were rejected after abstract screening and 32 after full-text reading. The 37 accepted articles resulted to address PI simulation in brain (n = 11), myocardial (n = 8), liver (n = 2), tumour (n = 1), finger (n = 1), and non-specific tissue (n = 14), with diverse modalities: ultrasound (n = 11), computed tomography (n = 11), magnetic resonance imaging (n = 17), and positron emission tomography (n = 2). Three phantom designs were described: basic (n = 6), aligned capillary (n = 22), and tissue-filled (n = 12). Microvasculature and tissue perfusion were combined in one compartment (n = 23) or in two separated compartments (n = 17). With the only exception of one study, inter-compartmental fluid exchange could not be controlled. Nine studies compared phantom results with human or animal perfusion data. Only one commercially available perfusion phantom was identified. Conclusion: We provided insights into contemporary phantom approaches to PI, which can be used for ground truth evaluation of quantitative PI applications. Investigators are recommended to verify and validate whether assumptions underlying PI phantom modelling are justified for their intended phantom application

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

Repeated, low-dose oral esketamine in patients with treatment-resistant depression:pilot study

Contains fulltext : 241981.pdf (Publisher’s version ) (Open Access

Oral esketamine for treatment-resistant depression:rationale and design of a randomized controlled trial

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016

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.

Correction to:Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

After publication of our article [1] we were notified that Figure 1 was wrongly presented