Noninvasive Studies Research Articles

Extended source analysis of movement related potentials (MRPs) for self-paced hand and foot movements demonstrates opposing cerebral and cerebellar laterality: a preliminary study

The cerebellum is known to have extensive reciprocal connectivity with the cerebral cortex, including with prefrontal and posterior parietal cortex, which play an important role on the planning and execution of voluntary movement. In the present article we report an exploratory non-invasive electrophysiological study of the activity of the cerebellum and cerebrum during voluntary finger and foot movements. In a sample of five healthy adult subjects, we recorded EEG and the electro-cerebellogram (ECeG) with a 10% cerebellar extension montage during voluntary left and right index finger and foot movements. EMG was recorded from finger extensors and flexors and from the tibialis anterior and soleus muscles and was used to generate triggers for movement related averaging (−2000 to +2000 ms). Source analysis was conducted over five epochs defined relative to EMG onset: whole epoch (−1000 to +1000 ms), pre-move 1000 (−1000 to 0 ms), pre-move 500 (−500 to 0 ms), post-move 500 (0 to +500 ms) and post-move 1000 (0 to +1000 ms). This yielded a total of 123 cerebral and 65 cerebellar dipole clusters from across all epochs, including the pre-movement epochs, which were then subject to statistical analysis. These demonstrated predominantly contralateral dominance for the cerebral clusters, but predominantly ipsilateral dominance for the cerebellar clusters. In addition, both cerebral and cerebellar clusters showed evidence of a somatotopic gradient, medially (X-axis) for the cerebral clusters, and medially and dorso-ventrally (Z-axis) for the cerebellar clusters. These findings support the value of recording cerebellar ECeG and demonstrate its potential to contribute to understanding cerebellar function.

Micro-scale particle tracking using hybrid detectors

Positron Emission Particle Tracking (PEPT) techniques allow the tracking of a radioactive tracer particle moving within a system of flow, enabling non-invasive study of dynamic systems. On the micro-scale, PEPT performance is limited by the achievable activity in radiolabelling a suitable tracer particle, and the fixed geometry of conventional detector systems. To enable application of PEPT towards these scales advanced instrumentation is required, and a hybrid detection system has been developed combining scintillator and semiconductor devices. A bismuth germanate oxide (BGO) scintillator array consisting of 1024 detector elements derived from CTI/Siemens PET scanners (512 pixels of 6.75 x 6.25 x 30 mm3 and 512 pixels of 4.1 x 4.0 x 30 mm3) forms a field of view of 150 x 196 x 101 mm3. A pair of pixelated cadmium zinc telluride room temperature semiconductors (9680 pixels of 1.8 x 1.8 x 0.5 mm3) form a high spatial resolution region of 62 x 42 x 20 mm3 placed within the larger field of view. The design choice maximizes absolute efficiency by merit of the scintillators and enhances spatial resolution through the semiconductors. Energy and timing resolutions of the BGO elements were determined, and sensitivity profiles of the system modelled numerically, enabling the characterization of the system absolute efficiency and spatial resolution. The results suggest the applicability of PEPT in the study of microscale flows for the first time, including investigating flows in capillaries and micro-fluidic devices.

Urologic manifestations of hypotonia, ataxia, and delayed development syndrome (HADDS), a rare neurodevelopmental disorder

Early B-cell factor 3 (EBF3) is a transcription factor involved in neuronal differentiation and maturation. Pathogenic variants are associated with hypotonia, ataxia, and delayed development syndrome (HADDS) (MIM#617330). Urologic manifestations are common and may have implications regarding long term renal function. To review all known patients with pathogenic variants of the EBF3 gene resulting in HADDS with urologic manifestations. We hypothesize a high rate of bladder dysfunction secondary to the EBF3 variant's impact on relaxation of the urinary sphincter leading to detrusor sphincter dyssynergia (DSD). The PubMed database was queried for publications of the EBF3 mutation between January 2017 and January 2023. Search terms were "EBF3 mutation OR HADDS AND urology OR phenotype". Retrospective analysis of HADDS patients cared for in our institution was performed. Demographic and clinical information was collected. We identified 52 patients (33F:19M) through literature (28F:18M) and retrospective review (5F:1M). There was a high prevalence of genitourinary physical exam abnormalities, history of urinary tract infection, vesicoureteral reflux (VUR), and diagnosis of neurogenic bladder. Within the literature review cohort, 67% had a urologic diagnosis. Females were disproportionately affected with urologic manifestations. In our cohort, four of six children were diagnosed with VUR and severe voiding dysfunction consistent with neurogenic bladder (67%). These children were managed with a vesicostomy. Five children had bowel dysfunction requiring therapy. Urodynamics suggested a high prevalence of external sphincter dyssynergia. Less severe forms of DSD were felt to be implicated in the abnormal voiding parameters in children who presented later in life based on non-invasive flow studies. There is significant variability in the phenotypic presentation of patients with HADDS. While EBF3 plays a clear role in neurodevelopment, it also impacts muscle development and may impact muscle relaxation. The location of the genetic variant may impact the degree of DSD, with more severe forms leading to earlier presentations. Initial work-up should include a renal ultrasound (RUS) and post void residual (PVR). Consideration can be given to obtaining a VCUG, DMSA scan or urodynamic studies. Yearly screening should be pursued with an RUS and PVR in those with an initial unremarkable work-up given the variable timing and severity of presentation. Urologic manifestations of HADDS include high rates of bladder dysfunction secondary to DSD, vesicoureteral reflux, urinary tract infection, and cryptorchidism. These patients are at risk of renal deterioration if urinary abnormalities are not properly diagnosed and managed.

Left ventricular endocardial activation maps during right ventricular pacing in pediatric patients.

Cardiac pacing from right ventricular (RV) sites may cause electromechanical ventricular dyssynchrony. Invasive and noninvasive mapping studies showed left ventricular (LV) activation sequence in adults. Aim of this study was to seek out the LV endocardial activation (LVEA) in pediatric patients who underwent RV pacing. Single-center, prospective study conducted on pediatric patients who underwent left sided catheter ablation of accessory pathways with the Carto Univu mapping system. After successful ablation procedures, LVEA was recorded by the ablation catheter during sinus rhythm (SR) and during para-hisian (PHP), midseptum (MSP), and apical (RVAP) pacing. Seventeen patients, 13 males, aged 12 (10-15) years, registered LV activation maps and times (LVAT). SR showed significantly shorter LVAT than during pacing. LVAT of PHP was shorter than MSP, while there were not significant differences among PHP and MSP versus RVAP. In SR initial LV endocardial activation occurred in two midseptum sites, inferior-posterior and superior-anterior. During PHP, initial activation occurred at parahisian basal septum, rapidly followed by midseptum as in SR. During MSP and RVAP initial activation occurred at midseptum and apex, respectively. From all initial sites, the excitation spreads toward the base of the lateral LV free wall. A mild linear correlation was found between QRS duration and LVAT for MSP and for PHP. In pediatric patients LVEA maps during RV pacing showed that the shortest LVAT was obtained with PHP. The LV activation pattern seemed similar in sinus rhythm, PHP and MSP, from midseptum to LV lateral base.

Non-Invasive Estimation of Central Systolic Blood Pressure by Radial Tonometry: A Simplified Approach.

Central systolic blood pressure (cSBP) provides valuable clinical and physiological information. A recent invasive study showed that cSBP can be reliably estimated from mean (MBP) and diastolic (DBP) blood pressure. In this non-invasive study, we compared cSBP calculated using a Direct Central Blood Pressure estimation (DCBP = MBP2/DBP) with cSBP estimated by radial tonometry. Consecutive patients referred for cardiovascular assessment and prevention were prospectively included. Using applanation tonometry with SphygmoCor device, cSBP was estimated using an inbuilt generalized transfer function derived from radial pressure waveform, which was calibrated to oscillometric brachial SBP and DBP. The time-averaged MBP was calculated from the radial pulse waveform. The minimum acceptable error (DCBP-cSBP) was set at ≤5 (mean) and ≤8 mmHg (SD). We included 160 patients (58 years, 54%men). The cSBP was 123.1 ± 18.3 mmHg (range 86-181 mmHg). The (DCBP-cSBP) error was -1.4 ± 4.9 mmHg. There was a linear relationship between cSBP and DCBP (R2 = 0.93). Forty-seven patients (29%) had cSBP values ≥ 130 mmHg, and a DCBP value > 126 mmHg exhibited a sensitivity of 91.5% and specificity of 94.7% in discriminating this threshold (Youden index = 0.86; AUC = 0.965). Using the DCBP formula, radial tonometry allows for the robust estimation of cSBP without the need for a generalized transfer function. This finding may have implications for risk stratification.

The Choroidal Vascularity Index Versus Optical Coherence Tomography Angiography in the Evaluation of the Choroid with a Focus on Age-Related Macular Degeneration.

The choroid is the most vascularized structure of the eye and it is fundamental for the trophism of the outer retina. Its proper functioning and homeostasis represent key points in maintaining normal retinal physiology. Choroidal alterations may be implicated in the development and progression of numerous pathologies; therefore, in-depth studies using imaging techniques can be of crucial relevance to understanding the pathophysiology of retinal-choroidal diseases. The advent of spectral-domain optical coherence tomography (SDOCT) has enabled the non-invasive study of the choroid in vivo and the most recent development, optical coherence tomography angiography (OCTA), allows for the high-resolution visualization of the choriocapillaris and the choroid in regard to vascularization. The choroidal vascularity index (CVI) is a new parameter calculated on SDOCT scans and is defined as the ratio of the luminal area to the total choroidal area. In this review, a study of the choroid using OCTA and CVI will be evaluated in depth and the pros and cons of these two methods will be analyzed, with a particular focus on age-related macular degeneration.

Electrophysiological findings in migraine may reflect abnormal synaptic plasticity mechanisms: A narrative review.

The cyclical brain disorder of sensory processing accompanying migraine phases lacks an explanatory unified theory. We searched Pubmed for non-invasive neurophysiological studies on migraine and related conditions using transcranial magnetic stimulation, electroencephalography, visual and somatosensory evoked potentials. We summarized the literature, reviewed methods, and proposed a unified theory for the pathophysiology of electrophysiological abnormalities underlying migraine recurrence. All electrophysiological modalities have determined specific changes in brain dynamics across the different phases of the migraine cycle. Transcranial magnetic stimulation studies show unbalanced recruitment of inhibitory and excitatory circuits, more consistently in aura, which ultimately results in a substantially distorted response to neuromodulation protocols. Electroencephalography investigations highlight a steady pattern of reduced alpha and increased slow rhythms, largely located in posterior brain regions, which tends to normalize closer to the attacks. Finally, non-painful evoked potentials suggest dysfunctions in habituation mechanisms of sensory cortices that revert during ictal phases. Electrophysiology shows dynamic and recurrent functional alterations within the brainstem-thalamus-cortex loop varies continuously and recurrently in migraineurs. Given the central role of these structures in the selection, elaboration, and learning of sensory information, these functional alterations suggest chronic, probably genetically determined dysfunctions of the synaptic short- and long-term learning mechanisms.

Состояние системы глазной поверхности у детей с аномалиями рефракции

Purpose. To evaluate subjective signs and objective clinical symptoms of disorders of the ocular surface system in children with refractive errors. Material and methods. 76 children (152 eyes) with ametropia aged 8 to 18 years were examined. All patients were divided into 2 groups: group 1 – 30 patients aged 8 to 11 years, group 2 – 46 patients aged 12 to 18 years. The severity of the subjective signs of the "dry eye" syndrome and the state of visual comfort were assessed using an online survey developed by the authors. Objectively, the state of the ocular surface system was examined by invasive methods (Schirmer I test, Schirmer II test, Norn test), as well as non-invasive methods using a keratograph (non-invasive tear breakup time, tear meniscus height, meibography, assessment of the severity of hyperemia of the bulbar conjunctiva). In 20 patients (40 eyes) osmometry of the lower lacrimal meniscus was performed. Results. According to a survey of 76 patients, 34 patients (44.7%) had minor disorders of the ocular surface system, 25 patients (32.9%) had moderate disorders, 7 patients (9.2%) had severe disorders, and 10 patients (13.2%) – significantly severe disorders. The indicators of the main tear secretion in the younger age group differ slightly from the standards, while in the older age group they exceed them by 2 mm, the total tear production in both groups of the study was slightly lower than the age standards. The obtained values of reflex tear production are sharply reduced in both study groups, at the age of 12–18 years the deviation is more significant. The average tear film osmolarity in the group of 20 patients aged 12–18 years was 302.75 mOsm/l, which corresponds with adult standards, however, in 6 patients from this group, the values exceeded the standards up to 332 mOsm/l, which is typical for moderate severity dry eye syndrome. It has been established that the indicators of tear film stability measured by both invasive and non-contact methods have similar values. In the group of children from 12 to 18 years old, the indicators are at the lower limit of the norm, however, the spread of the results indicates that there were patients with reduced indicators in the group. The number of eyes with loss of meibomian glands ducts of the 1st degree in the group of children aged 12–18 years was 31.5%, while in the younger group it was 26.7%. A mixed injection of the conjunctiva in the form of hyperemia of the 2nddegree was observed in 10.8% of the eyes in the older group, while in the other group only in 3.4% of the eyes. If more significant subjective chnges were detected, in combination with a deviation from the norms in clinical trials, it was advisable to prescribe age-appropriate drug therapy to patients to correct these conditions. Conclusion. When evaluating the subjective signs of a disorder of the state of the ocular surface system in children, special attention should be paid to the procedure for collecting an anamnesis and quantitative assessment of symptoms. Even in the absence of complaints, it is necessary to conduct an objective, preferably non-invasive study of the stability of the tear film, the state of the meibomian glands, and, if necessary, tear production. When a complex of subjective signs of moderate severity is detected, it is necessary to conduct an explanatory conversation with patients and their parents, paying attention to the aspects of eliminating risk factors for the development of disorders of the ocular surface system. Key words: ocular surface system, tear secretion, tear film stability, meibography

An Overview of Clinical Examinations in the Evaluation and Assessment of Arterial and Venous Insufficiency Wounds.

Arterial and venous insufficiency are two major causes of chronic wounds with different etiology, pathophysiology, and clinical manifestations. With recent advancements in clinical examination, clinicians are able to obtain an accurate diagnosis of the underlying disease, which plays an important role in the treatment planning and management of patients. Arterial ulcers are mainly caused by peripheral artery diseases (PADs), which are traditionally examined by physical examination and non-invasive arterial Doppler studies. However, advanced imaging modalities, such as computed tomography angiography (CTA) and indocyanine green (ICG) angiography, have become important studies as part of a comprehensive diagnostic process. On the other hand, chronic wounds caused by venous insufficiency are mainly evaluated by duplex ultrasonography and venography. Several scoring systems, including Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification, the Venous Clinical Severity Score (VCSS), the Venous Disability Score, and the Venous Segmental Disease Score (VSDS) are useful in defining disease progression. In this review, we provide a comprehensive overlook of the most widely used and available clinical examinations for arterial and venous insufficiency wounds.

An imbalance of excitation and inhibition in the multisensory cortex impairs the temporal acuity of audiovisual processing and perception.

The neural integration of closely timed auditory and visual stimuli can offer several behavioral advantages; however, an overly broad window of temporal integration-a phenomenon observed in various neurodevelopmental disorders-could have far-reaching perceptual consequences. Non-invasive studies in humans have suggested that the level of GABAergic inhibition in the multisensory cortex influences the temporal window over which auditory and visual stimuli are bound into a unified percept. Although this suggestion aligns with the theory that an imbalance of cortical excitation and inhibition alters multisensory processing, no prior studies have performed experimental manipulations to determine the causal effects of a reduction of GABAergic inhibition on audiovisual temporal perception. To that end, we used a combination of in vivo electrophysiology, neuropharmacology, and translational behavioral testing in rats to provide the first mechanistic evidence that a reduction of GABAergic inhibition in the audiovisual cortex is sufficient to disrupt unisensory and multisensory processing across the cortical layers, and ultimately impair the temporal acuity of audiovisual perception and its rapid adaptation to recent sensory experience. Looking forward, our findings provide support for using rat models to further investigate the neural mechanisms underlying the audiovisual perceptual alterations observed in neurodevelopmental disorders, such as autism, schizophrenia, and dyslexia.

Ethics of prenatal diagnosis choice: a comparison of approaches

The article discusses various methods of prenatal diagnosis and the ethical issues they raise. Currently, prenatal diagnosis is an actively developing area of medicine. There are invasive and noninvasive studies, moreover, non-invasive studies are assigned to all pregnant women without exception, and invasive studies are strictly according to the doctor's indications due to the high likelihood of complications. In addition, a non-invasive prenatal genetic test (NIPT) is available to pregnant women in Russia as part of VHI. Particular attention is paid to the ethical aspects of this particular study, which is actively gaining popularity among the population in large cities of Russia.

A Prospective Non-Randomised Interventional Study of Goal-Directed Ultrafiltration Compared With Clinical Dry-Weight Assessment in Achieving Euvolemic Status of Patients on Maintenance Hemodialysis

An accurate assessment of intravascular volume status in hemodialysis (HD) patients presents a significant challenge. Current clinical practices to determine dry weight is flawed due to interobserver variability and nonreproducibility. This miscalculation results in either chronic hypervolemia or hypovolemia with intra or interdialytic hypotension. The quest for noninvasive volume assessment tools to aid in the estimation of dry weight still continues. This study aims at goal-directed ultrafiltration removal compared with clinical dry-weight assessment in achieving euvolemic status of patients on chronic HD. It is a prospective, single-centered, nonrandomized, noninvasive interventional study on HD patients, for 12 months. Fifty two patients participated out of which 46 completed the study. Ultrasound-guided inferior vena cava collapsing index (IVCCI) and B lines were measured at intervals along with cardiac parameters. Dry weight was first estimated clinically by trial and error method. New dry weight target was set when B-lines were less than four in the eight site lung ultrasound and IVCCI between 50 and 75%, after 30 min post dialysis. Approximately 23.9% of the patients did not require dry-weight modification throughout the study. About 19% patients did not achieve dry weight in spite of all interventions. Overall, 56.5% of the patients achieved dry weight during the study period. A total of 46.3% of patients with NYHA Grade 3 dyspnoea observed at the start of study was reduced to 2.2%, showing statistical significance. Clinical assessment when bundled with noninvasive technology of assessment of dry weight showed encouraging results. B-lines and IVCCI estimation could be additional tools to achieve target weight goals, reducing complications and increasing compliance.

Analysis of Correlation between Anthropometry of Hand and Smartphone Overuse on Musculoskeletal Pain in Thumb/Wrist in Medical Students: A Cross Sectional Study at Tertiary Care Center of Central India

Introduction: As mobile technology has evolved and is used extensively by most of the population, there is an increase in incidences of pain associated with the overuse of mobile phones. Pain associated with smartphone use is because of prolonged periods of time engaging with digital devices. The use of smartphones can cause various types of physical discomforts, such as neck pain, shoulder pain, and thumb pain, collectively referred to as “smartphone-related musculoskeletal disorders” (SRMDs). These medical issues arise mainly due to poor posture, repetitive movements, and prolonged use of smartphones without breaks. The impact of SRMDs on an individual’s daily life can be significant, resulting in decreased productivity, reduced quality of life, and increased healthcare costs. It is important for individuals to be aware of the risks associated with smartphone use and take steps to minimize their risk of developing SRMDs. Methods: The proposed study was an observational, questionnaire-based non-invasive study. The study was conducted in AIIMS Bhopal. The study was conducted on 130 adult males and 70 adult females. Personal and demographic details along with anthropometric measurements like Palm length, Palm breadth, and middle finger length were recorded. The level of smartphone addiction of individuals was also documented. Results: Correlations among palm length, palm breadth, length of the middle finger, smartphone size and shape, addiction level, and musculoskeletal pain were calculated. Conclusion: Present study proposes some important remedies which may minimize the musculoskeletal pain associated with the overuse of mobile phones.

P-722 Impact of blastocyst quality and post-thaw embryo culture factors in non-invasive PGT-A informativity on vitrified blastocysts.

Abstract Study question What are the most important factor/s involved in the informativity of non-invasive PGT-A (niPGT-A) of vitrified blastocysts? Summary answer The day of vitrification and post-thaw time in culture of vitrified blastocysts are the most important factors for niPGT-A informativity, without correlation with blastocyst quality. What is known already niPGT-A is a technique that allows the non-invasive study of the chromosomal content of blastocysts. The informativity and concordance rates for fresh (Rubio, 2020) and frozen-thawed embryos (Garcia-Pascual, 2022) have been related with the time in culture and the day of media collection. However, there is a need to understand the optimal conditions needed to obtain optimal informativity for frozen-thawed vitrified blastocyst undergoing niPGT-A. Study design, size, duration Prospective study including 135 spent blastocyst media (SBM) and the corresponding blastocyst samples from thawed day-5 and day-6 blastocysts from PGT-A (73) and niPGT-A (62) cycles collected from January 2021 until March 2022. Blastocysts were discarded under IRB approval. The embryos were divided into 3 groups depending on the day of development and the time in culture after thawing: group-1, day-5 blastocysts cultured 8h; group-2, day-5 blastocysts cultured 24h and group-3, day-6 blastocysts cultured 8h. Participants/materials, setting, methods Media and blastocysts were obtained from IVF patients (29-42 years-old). After thawing, each blastocyst was washed to remove remaining cumulus cells and individually transferred to a 10 μL droplet of fresh media or to an EmbryoScope dish with 20 μL per well. SBM and blastocysts were collected, frozen and analysed by Next Generation Sequencing. Correlation between concordance rates (overall agreement between SBM and blastocyst samples), informativity, embryo quality and time in culture were evaluated. Main results and the role of chance All the embryos had a good embryo quality (BB or greater using Gardner Criteria) but different expansion degree. Informativity was significantly lower when day-5 embryos were cultured for only 8 hours (group 1), regardless of the degree of expansion (expansion degree 3, 28.57%; degree 4, 64.29% and degree 5-6, 57.14%, p < 0.0005). The concordance rates between SBM and whole blastocysts were very high and no significant different in relation to the expansion degree when comparing day-5 embryos cultured for 8 hours (group 1, 90.5%) with 24 hours (group 2, 93.6%) or with day-6 embryos cultured for 8 hours (group 3, 92.3%). The data suggest that the important factor impacting the informativity rate is the day of vitrification, and the time in culture after thawing, but not the expansion degree of the embryos. Regarding the concordance rates, there is no impact of the time in culture nor the expansion degree. Limitations, reasons for caution The main limitation of this study is that all the embryos analysed had fair or good quality but different expansion degrees. Wider implications of the findings The high concordance rates observed in frozen blastocysts opens the possibility of expanding the use of niPGT-A to frozen blastocyst without an impact of the expansion degree in the results. Trial registration number Not applicable

Machine-Learning Methods for Speech and Handwriting Detection Using Neural Signals: A Review

Brain–Computer Interfaces (BCIs) have become increasingly popular in recent years due to their potential applications in diverse fields, ranging from the medical sector (people with motor and/or communication disabilities), cognitive training, gaming, and Augmented Reality/Virtual Reality (AR/VR), among other areas. BCI which can decode and recognize neural signals involved in speech and handwriting has the potential to greatly assist individuals with severe motor impairments in their communication and interaction needs. Innovative and cutting-edge advancements in this field have the potential to develop a highly accessible and interactive communication platform for these people. The purpose of this review paper is to analyze the existing research on handwriting and speech recognition from neural signals. So that the new researchers who are interested in this field can gain thorough knowledge in this research area. The current research on neural signal-based recognition of handwriting and speech has been categorized into two main types: invasive and non-invasive studies. We have examined the latest papers on converting speech-activity-based neural signals and handwriting-activity-based neural signals into text data. The methods of extracting data from the brain have also been discussed in this review. Additionally, this review includes a brief summary of the datasets, preprocessing techniques, and methods used in these studies, which were published between 2014 and 2022. This review aims to provide a comprehensive summary of the methodologies used in the current literature on neural signal-based recognition of handwriting and speech. In essence, this article is intended to serve as a valuable resource for future researchers who wish to investigate neural signal-based machine-learning methods in their work.

Non-Invasive Study of the Pigments of a Painting on Copper with the Inscription “Boceto di Pablo Veronese” on the Back

The palette used on a small painting on copper support, with the inscription “Boceto di Pablo Veronese” on the back, was characterized. Non-invasive techniques such as X-ray diffraction (XRD) and hand-held X-ray fluorescence (XRF) were proven to be highly effective for this. The objectives of the proposed work were twofold. On the one hand, the objective was the study, in situ, of the pigments of a painting on a copper support. On the other hand, it was to enrich the literature related to the study of paintings on metal supports, since few related studies are available despite the relatively large number of such 16th and 17th century paintings from Italy and Northern Europe. The results of the analysis showed a copper support with a base layer of gypsum mixed with ochre earths. Atop this layer is a sketch with lead white in the lighter areas and bone black in the darker shadow areas, suggesting that the artist performed a preliminary study of the luminosity of the scene. Finally, the upper or pictorial layer consists of a mix of pigments with some lead white to lower saturation and increase lightness, particularly evident in the flesh tones. The resulting palette thus includes lead white, vermilion, bone black, Naples yellow, and lazurite pigments. These results are compared to Veronese’s other paintings, as well as to those of certain contemporary artists, and the use of the resulting pigments in 16th and 17th century Italian painting techniques is discussed.

Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT) for NonInvasive Whole-Brain Imaging of Ischemic Stroke.

Presented here is an experimental ischemic stroke study using our newly developed noninvasive imaging system that integrates three acoustic-based imaging technologies: photoacoustic, ultrasound, and angiographic tomography (PAUSAT). Combining these three modalities helps acquire multi-spectral photoacoustic tomography (PAT) of the brain blood oxygenation, high-frequency ultrasound imaging of the brain tissue, and acoustic angiography of the cerebral blood perfusion. The multi-modal imaging platform allows the study of cerebral perfusion and oxygenation changes in the whole mouse brain after stroke. Two commonly used ischemic stroke models were evaluated: the permanent middle cerebral artery occlusion (pMCAO) model and the photothrombotic (PT) model. PAUSAT was used to image the same mouse brains before and after a stroke and quantitatively analyze both stroke models. This imaging system was able to clearly show the brain vascular changes after ischemic stroke, including significantly reduced blood perfusion and oxygenation in the stroke infarct region (ipsilateral) compared to the uninjured tissue (contralateral). The results were confirmed by both laser speckle contrast imaging and triphenyltetrazolium chloride (TTC) staining. Furthermore, stroke infarct volume in both stroke models was measured and validated by TTC staining as the ground truth. Through this study, we have demonstrated that PAUSAT can be a powerful tool in noninvasive and longitudinal preclinical studies of ischemic stroke.

Monitoring Muscle Perfusion in Rodents During Short-Term Ischemia Using Power Doppler Ultrasound.

The aim of this work was to evaluate the reliability of power Doppler ultrasound (PD-US) measurements made without contrast enhancement to monitor temporal changes in peripheral blood perfusion. On the basis of pre-clinical rodent studies, we found that combinations of spatial registration and clutter filtering techniques applied to PD-US signals reproducibly tracked blood perfusion in skeletal muscle. Perfusion is monitored while modulating hindlimb blood flow. First, in invasive studies, PD-US measurements in deep muscle with laser speckle contrast imaging (LSCI) of superficial tissues made before, during and after short-term arterial clamping were compared. Then, in non-invasive studies, a pressure cuff was employed to generate longer-duration hindlimb ischemia. Here, B-mode imaging was also applied to measure flow-mediated dilation of the femoral artery while, simultaneously, PD-US was used to monitor downstream muscle perfusion to quantify reactive hyperemia. Measurements in adult male and female mice and rats, some with exercise conditioning, were included to explore biological variables. PD-US methods are validated through comparisons with LSCI measurements. As expected, no significant differences were found between sexes or fitness levels in flow-mediated dilation or reactive hyperemia estimates, although post-ischemic perfusion was enhanced with exercise conditioning, suggesting there could be differences between the hyperemic responses of conduit and resistive vessels. Overall, we found non-contrast PD-US imaging can reliably monitor relative spatiotemporal changes in muscle perfusion. This study supports the development of PD-US methods for monitoring perfusion changes in patients at risk for peripheral artery disease.

Correlations between capillary density and degree of skin pigmentation in healthy children analysed by nailfold video capillaroscopy.

Nailfold video capillaroscopy (NVC) is a simple, non-invasive diagnostic tool but studies with normal values for capillary density in healthy children are rare. Ethnic background seems to play a role in capillary density; however, this is not well substantiated yet. In this work, we set out to evaluate influence of ethnic background/skin pigmentation and age on capillary density reading in healthy children. Secondary aim was to investigate whether there is a significant difference in density between different fingers within the same patient. Between 2016 and 2021, healthy children from schools around AUMC were approached, by convenience sampling. In this cross-sectional study, capillaroscopic images were obtained in a one-time videocapillaroscopy (×200 magnification) addressing the capillary density (i.e., number of capillaries per linear millimetre in the distal row). This parameter was compared to age, sex, ethnicity, skin pigment grade (I-III) and between eight different fingers, excluding the thumbs. Density differences were compared by ANOVAs. Correlations between capillary density and age were calculated with Pearson correlations. We investigated 145 healthy children with mean age of 11.03 years (SD 3.51). The range of capillary density was 4-11 capillaries per millimetre. We observed a lower capillary density in the 'grade II' (6.4±0.5 cap/mm, P<0.001) and 'grade III' (5.9±0.8 cap/mm, P<0.001) pigmented-classified groups compared to the 'grade I' group (7.0±0.7 cap/mm). We did not find a significant correlation between age and density in the overall group. The fifth fingers on both sides had a significantly lower density compared to the other fingers. Healthy children <18 years with higher degree of skin pigmentation show a significantly lower nailfold capillary density. In subjects with an African/Afro-Caribbean and North-African/Middle-Eastern ethnicity, a significantly lower mean capillary density was observed compared to subjects with the Caucasian ethnicity (P<0.001, and P<0.05, respectively. There were no significant differences between other ethnicities. No correlation was found between age and capillary density. The fifth fingers on both hands displayed lower capillary density compared to the other fingers. This needs to be taken into account when describing lower density in paediatric patients with connective tissue diseases.

Challenges of copro-parasitological surveys in wild Iberian ibex (Capra pyrenaica) populations addressed through a combination of molecular and statistical tools.

Copro-parasitological surveys in wildlife face challenges due to the secretive nature of many species and the unknown performance of the diagnostic tests employed. To overcome these issues, we used a combination of hierarchical models (site-occupancy and N-mixture models) applied to copro-parasitological data obtained from fecal samples assigned to the host species by molecular methods in the Iberian ibex in north-western Iberian Peninsula. The aims were to compare the performance of four diagnostic tests (Mini-FLOTAC, McMaster, Willis flotation, and natural sedimentation) and to use this methodological approach (molecular analysis with hierarchical models) to better estimate positivity proportion and shedding intensity in a wild ibex population. Pooled fecal samples were collected, and those confirmed by molecular analyses to be the host species in question were included in the study. Hierarchical models confirmed different performances of each diagnostic test, with Mini-FLOTAC showing higher sensitivity for eimeriid coccidia, Willis flotation (for proportion positive) and McMaster (for shedding intensity) in gastrointestinal Strongylida, and equal performance of MiniFlotac/Willis flotation (for proportion positive) and MiniFlotac/McMaster (for shedding intensity) in Moniezia spp. This study employed a combination of molecular and statistical methods that improved the estimates of prevalence and shedding intensity and allowed us to compare the performance of four diagnostic tests while assessing the effect of covariates. Such improvements are critical to enhancing inference in non-invasive wildlife copro-parasitological studies.