The Influence of Acoustic Impedance Mismatch on Post-Stenotic Pulsed-Doppler Ultrasound Measurements in a Coronary Artery Model

Acoustic impedance mismatch at the fluid-wall interface was shown to affect the spectra from an intravascular Doppler device in an in vitro model with a diameter typical of human coronary arteries. Measurements were obtained first under Poiseuille flow conditions with impedance mismatches of 0%, 7% and 12%, and then under stenosed conditions for the 0% and 7% mismatch cases. For the zero mismatch case, the Doppler spectra could be readily interpreted in terms of fluid mechanical phenomena. When mismatch was present, the spectra from Poiseuille flow exhibited multiple peaks which could not be directly related to the velocity profile. Also, the spectra from stenosed flow with a mismatch of 7% were similar to those from the zero mismatch case but did not exhibit the specific flow-related features as clearly. These results indicate that the impedance mismatch alters the acoustic environment inside the model and that this causes artifact in the Doppler spectra

Slice Location Dependence of Aortic Regurgitation Measurements with MR Phase Velocity Mapping

Although several methods have been used clinically to assess aortic regurgitation (AR), there is no “gold standard” for regurgitant volume measurement. Magnetic resonance phase velocity mapping (PVM) can be used for noninvasive blood flow measurements. To evaluate the accuracy of PVM in quantifying AR with a single imaging slice in the ascending aorta, in vitro experiments were performed by using a compliant aortic model. Attention was focused on determining the slice location that provided the best results. The most accurate measurements were taken between the aortic valve annulus and the coronary ostia where the measured (Y) and actual (X) flow rate had close agreement (Y = 0.954 × + 0.126, r2 = 0.995, standard deviation of error = 0.139 L/min). Beyond the coronary ostia, coronary flow and aortic compliance negatively affected the accuracy of the measurements. In vivo measurements taken on patients with AR showed the same tendency with the in vitro results. In making decisions regarding patient treatment, diagnostic accuracy is very important. The results from this study suggest that higher accuracy is achieved by placing the slice between the aortic valve and the coronary ostia and that this is the region where attention should be focused for further clinical investigation

Quantification of Mitral Regurgitation With MR Phase-Velocity Mapping Using a Control Volume Method

Reliable diagnosis and quantification of mitral regurgitation are important for patient management and for optimizing the time for surgery. Previous methods have often provided suboptimal results. The aim of this in vitro study was to evaluate MR phase-velocity mapping in quantifying the mitral regurgitant volume (MRV) using a control volume (CV) method. A number of contiguous slices were acquired with all three velocity components measured. A CV was then selected, encompassing the regurgitant orifice. Mass conservation dictates that the net inflow into the CV should be equal to the regurgitant flow. Results showed that a CV, the boundary voxels of which excluded the region of flow acceleration and aliasing at the orifice, provided accurate measurements of the regurgitant flow. A smaller CV provided erroneous results because of flow acceleration and velocity aliasing close to the orifice. A large CV generally provided inaccurate results because of reduced velocity sensitivity far from the orifice. Aortic outflow, orifice shape, and valve geometry did not affect the accuracy of the CV measurements. The CV method is a promising approach to the problem of quantification of the MRV

Evaluation of the Precision of Magnetic Resonance Phase Velocity Mapping for Blood Flow Measurements

Evaluating the in vivo accuracy of magnetic resonance phase velocity mapping (PVM) is not straightforward because of the absence of a validated clinical flow quantification technique. The aim of this study was to evaluate PVM by investigating its precision, both in vitro and in vivo, in a 1.5 Tesla scanner. In the former case, steady and pulsatile flow experiments were conducted using an aortic model under a variety of flow conditions (steady: 0.1–5.5 L/min; pulsatile: 10–75 mL/cycle). In the latter case, PVM measurements were taken in the ascending aorta of ten subjects, seven of which had aortic regurgitation. Each velocity measurement was taken twice, with the slice perpendicular to the long axis of the aorta. Comparison between the measured and true flow rates and volumes confirmed the high accuracy of PVM in measuring flow in vitro (p \u3e 0.85). The in vitro precision of PVM was found to be very high (steady: y = 1.00x + 0.02, r = 0.999; pulsatile: y = 0.98x + 0.72, r = 0.997; x: measurement #1, y: measurement #2) and this was confirmed by Bland-Altman analysis. Of great clinical significance was the high level of the in vivo precision (y = 1.01x − 0.04, r = 0.993), confirmed statistically (p = 1.00). In conclusion, PVM provides repeatable blood flow measurements. The high in vitro accuracy and precision, combined with the high in vivo precision, are key factors for the establishment of PVM as the “gold-standard” to quantify blood flow

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa\u27s effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered

Preclinical in vivo longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic

In vivo biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-β pathology as well as its effects on downstream processes associated with Alzheimer’s disease pathophysiology. Here, we applied an in vivo longitudinal study design combined with imaging and cerebrospinal fluid biomarkers, mirroring those used in human clinical trials to assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in the McGill-R-Thy1-APP transgenic rat model. The bi-functional fusion protein consisted of a blood-brain barrier crossing single domain antibody (FC5) fused to an amyloid-β oligomer-binding peptide (ABP) via Fc fragment of mouse IgG (FC5-mFc2a-ABP). A five-week treatment with FC5-mFc2a-ABP (loading dose of 30 mg/Kg/iv followed by 15 mg/Kg/week/iv for four weeks) substantially reduced brain amyloid-β levels as measured by positron emission tomography and increased the cerebrospinal fluid amyloid-β42/40 ratio. In addition, the 5-week treatment rectified the cerebrospinal fluid neurofilament light chain concentrations, resting-state functional connectivity, and hippocampal atrophy measured using magnetic resonance imaging. Finally, FC5-mFc2a-ABP (referred to as KG207-M) treatment did not induce amyloid-related imaging abnormalities such as microhemorrhage. Together, this study demonstrates the translational values of the designed preclinical studies for the assessment of novel therapies based on the clinical biomarkers providing tangible metrics for designing early-stage clinical trials

What parameters affect left ventricular diastolic flow propagation velocity? in vitro studies using color m-mode doppler echocardiography

BACKGROUND: Insufficient data describe the relationship of hemodynamic parameters to left ventricular (LV) diastolic flow propagation velocity (Vp) measured using color M-mode Doppler echocardiography. METHODS: An in vitro LV model used to simulate LV diastolic inflow with Vp measured under conditions of varying: 1) Stroke volume, 2) heart rate (HR), 3) LV volume, 4) LV compliance, and 5) transmitral flow (TMF) waveforms (Type 1: constant low diastasis flow and Type 2: no diastasis flow). RESULTS: Univariate analysis revealed excellent correlations of Vp with stroke volume (r = 0.98), LV compliance (r = 0.94), and HR with Type 1 TMF (r = 0.97). However, with Type 2 TMF, HR was not associated with Vp. LV volume was not related to Vp under low compliance, but inversely related to Vp under high compliance conditions (r = -0.56). CONCLUSION: These in vitro findings may help elucidate the relationship of hemodynamic parameters to early diastolic LV filling

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

KCNT1- related epilepsy: An international multicenter cohort of 27 pediatric cases

ObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1- related epilepsy and explored genotype- phenotype correlations associated with frequently encountered variants.MethodsA cross- sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty- seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two- thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray- white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%- 50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence- based practice is still unavailable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/1/epi16480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/2/epi16480.pd