Sensitive Detection of Oral Leukoplakia: Analyzing P90 Biomarkers in Saliva and Tissue.

Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device's performance was optimized through characteristic tests. Human sample testing validated the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues.

Chronic oral diseases secondary to COVID-19 infection or vaccination: clinical cases and a narrative review.

OBJECTIVES: Autoimmune activation by COVID-19 infection/vaccination has been postulated to be responsible for initiating or reactivating multiple types of oral mucosal immune disorders. These include: oral lichen planus; oral pemphigoid; either bullous pemphigoid or mucous membrane pemphigoid with oral involvement; pemphigus vulgaris with oral involvement; and Sjögren disease. In addition, chronic conditions such as oral burning, xerostomia, or changes in taste and/or smell have also been linked to COVID-19 infection/vaccination. DATA SOURCES: Part 1 (mucosal conditions): an English-language literature review of Pubmed, Web of Science, Scopus, and Embase was performed searching cases of oral lichen planus, oral bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, and COVID-19 infection/vaccination, with additional cases from the authors' clinical practice presented. Part 2 (nonmucosal conditions): Cases of initiated or flared Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors' clinical practice were aggregated. RESULTS: The literature review discovered 29 cases of oral lichen planus following COVID-19 infection/vaccination. For bullous pemphigoid, 10 cases were identified after infection/vaccination. The number of pemphigus vulgaris cases following infection/vaccination was 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Nonmucosal disease: Sjögren disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination cases totaled 12 cases identified from the authors' clinical practice, with the majority occurring after infection. CONCLUSIONS: Chronic conditions after infection with COVID-19 or vaccination remain relatively rare and self-limited, yet reinforce the importance of comprehensive history taking involving COVID-19 to differentiate potential etiologic factors for these conditions.

Prevalence of acute periapical abscesses in head and neck cancer patients receiving radiotherapy.

AIMS: Head and neck cancer is a serious condition affecting the life of patients. Radiotherapy is commonly used to treat such conditions. The aim of this study was to assess the prevalence of acute periapical abscesses (PAs) in patients who received radiotherapy for head and neck cancer. METHODS AND RESULTS: Data on acute PAs and oropharyngeal cancer (OPC) diagnosis with or without a history of radiation therapy (RAD) was retrieved by searching the appropriate query in the database. All cases were diagnosed for acute PAs by calibrated dentists for patients admitted to urgent care. The odds ratio (OR) for the prevalence of acute PAs and its association with a history of OPC with or without RAD were then calculated. Adjustment for comorbidities such as diabetes, smoking and gingival and periodontal diseases was also done. The prevalence of acute PAs in patients with a history of OPC was significantly higher as compared to the general hospital patient population (OR 2.92, 95%CI, p < .0001). Males were more affected than females and whites were more affected than African Americans and other ethnicities. The prevalence for PAs in patients with a history of OPC and RAD was higher and the difference in prevalence was statistically significant (OR 3.61, 95%CI, p < .0001). Whites were more affected than African Americans by more than 3.5-fold. Adjustment for diabetes comorbidly affected mainly the OPC + RAD group, however, the difference remained statistically significant. Adjustment for smoking and gingival and periodontal disease reduced the OR but the difference remained statistically different. CONCLUSIONS: The high prevalence of acute PAs in patients with a history of OPC and RAD may suggest an association between these conditions warranting a meticulous medical and dental examination.

Improving sub-pixel accuracy in ultrasound localization microscopy using supervised and self-supervised deep learning.

With a spatial resolution of tens of microns, ultrasound localization microscopy (ULM) reconstructs microvascular structures and measures intravascular flows by tracking microbubbles (1-5 µm) in contrast enhanced ultrasound (CEUS) images. Since the size of CEUS bubble traces, e.g. 0.5-1 mm for ultrasound with a wavelength λ = 280 µm, is typically two orders of magnitude larger than the bubble diameter, accurately localizing microbubbles in noisy CEUS data is vital to the fidelity of the ULM results. In this paper, we introduce a residual learning based supervised super-resolution blind deconvolution network (SupBD-net), and a new loss function for a self-supervised blind deconvolution network (SelfBD-net), for detecting bubble centers at a spatial resolution finer than λ/10. Our ultimate purpose is to improve the ability to distinguish closely located microvessels and the accuracy of the velocity profile measurements in macrovessels. Using realistic synthetic data, the performance of these methods is calibrated and compared against several recently introduced deep learning and blind deconvolution techniques. For bubble detection, errors in bubble center location increase with the trace size, noise level, and bubble concentration. For all cases, SupBD-net yields the least error, keeping it below 0.1 λ. For unknown bubble trace morphology, where all the supervised learning methods fail, SelfBD-net can still maintain an error of less than 0.15 λ. SupBD-net also outperforms the other methods in separating closely located bubbles and parallel microvessels. In macrovessels, SupBD-net maintains the least errors in the vessel radius and velocity profile after introducing a procedure that corrects for terminated tracks caused by overlapping traces. Application of these methods is demonstrated by mapping the cerebral microvasculature of a neonatal pig, where neighboring microvessels separated by 0.15 λ can be readily distinguished by SupBD-net and SelfBD-net, but not by the other techniques. Hence, the newly proposed residual learning based methods improve the spatial resolution and accuracy of ULM in micro- and macro-vessels.

Maxillary Sinusitis Induced by Medication-Related Osteonecrosis of the Jaw.

The involvement of maxillary sinuses in patients taking bone-related medications has not been comprehensively considered in the literature, mostly dental. Considering the fact that paranasal sinuses are often captured in dental radiographs, it is incumbent upon dental practitioners to recognize abnormal presentations in the paranasal sinuses to ensure the appropriate management of medication-related osteonecrosis of the jaw (MRONJ). We present a case of a giant cell tumor (GCT) with atypical chronic sinusitis manifestation leading to MRONJ.

Increased odds for COVID-19 infection among individuals with periodontal disease.

OBJECTIVES: Periodontal disease has been linked to multiple systemic conditions, but the relationship with COVID-19 still needs to be elucidated. We hypothesized that periodontal disease may be associated with COVID-19 infection. MATERIALS AND METHODS: This study utilized cross-sectional data to establish the strength of the association between periodontal disease and COVID-19 infection. The University of Florida Health Center's i2b2 patient's registry was used to generate patient counts through ICD-10 diagnostic codes. Univariate descriptive statistics of the patient population and logistic regression to estimate odds ratios of associations between periodontal disease and COVID-19 infection were used for analysis. RESULTS: Patients with periodontal disease were 4.4 times more likely to be positively diagnosed with COVID-19 than patients without PD. Associations remained similar and robust (P value < 0.0001) after adjustment for age (OR = 4.34; 95% CI, 3.68-5.09), gender (OR = 4.46; 95% CI, 3.79-5.23), and smoking status (OR = 4.77; 95% CI, 4.04-5.59). Associations were smaller but remained robust (P value < 0.0001) after adjusting for race (OR = 2.83; 95% CI, 2.40-3.32), obesity (OR = 2.53; 95% CI, 2.14-2.98), diabetes (OR = 3.32; 95% CI, 2.81-3.90), and cardiovascular disease (OR = 2.68; 95% CI, 2.27-3.14). CONCLUSIONS: Periodontal disease is significantly associated with increased odds for COVID-19 infection. CLINICAL RELEVANCE: With the caveat of a cross-sectional study design, these results suggest that periodontal disease may increase the odds for COVID-19 infection.

Effect of Selective Serotonin Reuptake Inhibitor (Paroxetine) on Newly Formed Bone Volume: Real-Time In Vivo Micro-computed Tomographic Analysis.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety. The purpose of this study was to assess in real time the effect of paroxetine, an SSRI, on newly formed bone volume (NFBV) in standardized calvarial defects (SCDs) in rats. METHODS: Fourteen Wistar albino female rats with a mean age of 7.5 months and a mean weight of 275 g were used. The animals were randomly divided into 2 groups. The experimental group was given paroxetine 8 weeks before the surgical procedure and throughout the experiment, and the control group was given a placebo 8 weeks before the surgical procedure and throughout the experiment. In each group, 14 SCDs measuring 4.6 mm in diameter were created on the parietal bone. In both groups, a Bio-Oss + collagen membrane was placed. All defects showed primary closure. The volume of the newly formed bone (NFBV) was measured using in vivo micro-computed tomographic imaging. Measurements were taken at days 0, 14, 28, 42, and 56 after surgery using real-time assessment with micro-computed tomographic imaging. RESULTS: The mean NFBV was 17.12 ± 4.52 mm3 and 12.52 ± 4.78 mm3 for the control and experimental groups, respectively, at day 56. The differences between the 2 groups were statistically significant (P < .05) at all time intervals. CONCLUSIONS: Paroxetine intake significantly reduced the amount of regenerated NFBV and the rate of new bone formation.

Serotonin and norepinephrine reuptake inhibitors association with dry mouth in a hospital population.

OBJECTIVES: Xerostomia, or dry mouth, is a condition that results from the reduction or absence of saliva flow secondary to the use of certain medications. The objective of the present study was to analyze the relationship between xerostomia patients and the consumption of serotonin norepinephrine reuptake inhibitors (SNRIs). METHOD AND MATERIALS: The University of Florida (UF) Integrated Data (IDR) i2b2, for the period of June 2015 to September 2022, was used based on aggregates of the International Classification of Diseases 10th edition (ICD-10) diagnoses of dry mouth and use of SNRI. MedCalc Software was used to calculate odds ratios. RESULTS: The odds ratio for dry mouth in the SNRI group was 5.95 (95% CI 5.47 to 6.48, P < .0001). The odds ratio for dry mouth in females on SNRI was 5.48 (95% CI 4.97 to 6.02, P < .0001), for males 5.48 (95% CI 4.56 to 6.95), P < .0001), for children 2.87 (95% CI 1.19 to 6.96, P = .0192), and for adults 4.46 (95% CI 4.09 to 4.86, P < .0001). When the different SNRIs were analyzed separately, the odds ratio for dry mouth with the use of venlafaxine was 5.83 (95% CI 5.12 to 6.6, P < .0001), duloxetine 6.97 (95% CI 6.33 to 7.67, P <.0001), desvenlafaxine 5.24 (95% CI 3.65 to 7.52, P < .0001), and milnacipran 9.61 (95% CI 5.66 to 16.31, P < .0001). CONCLUSION: According to the present study, patients who are taking SNRIs are five-fold more likely to develop dry mouth compared to those not on medications. The results could be informative to medical professionals who prescribe SNRIs and who are not currently aware of the effect they have on salivary production and therefore quality of life, as well as the dental practitioners treating these patients with dry mouth sequalae. (Quintessence Int 2023;54:150-154; doi: 10.3290/j.qi.b3704403).

Effects of Crude Oil Properties and Dispersant on the Microstructure and Viscosity of Seawater-in-Oil Emulsions.

This study examines the effects of crude oil properties and dispersant concentration (Corexit 9500) on the evolution of bulk viscosity, viscoelastic properties, and microstructure of salt water-in-crude oil emulsions. Microscopy, followed by machine-learning-based analysis, provides the size and spatial distribution of the seawater droplets. The crude oils include light Bakken, Alaskan North Slope (ANS), and Louisiana oils, and medium to heavy Platform Henry, Cold Lake, and Platform Gina oils. The light and medium oils entrain water up to 80% by volume, and the heavy oils, up to 25%. The droplet sizes and distance between them decrease with increasing viscosity, with small droplets clustering around larger ones. The Bakken- and ANS-based emulsions are unstable, but all of the emulsions evolve in time. All exhibit a non-Newtonian behavior, with the viscosity decreasing with increasing shear rate. The storage modulus is higher than the loss modulus for light oils, and vice versa for heavy oils. Trends of their nondimensional viscosity are collapsed onto two power laws as a function of the Ohnesorge number involving the properties of the original oil, and the size or distance between droplets. For light oils, the power law exponent decreases with increasing capillary number based on the rheometer shear rate and increases for heavy oils. At high shear rates, the exponents converge to the same value, 0.45, suggesting that the oil viscosity becomes the property that defines the emulsion rheology. The present findings are consistent with previously published data. Premixing the emulsions with dispersant causes separation of most of the water from the light oils, leaving only sparse droplet concentrations. In contrast, owing to slow diffusion rate, only a small fraction of the seawater is extracted from the heavy oil emulsions. Hence, the sparse light oil emulsions become Newtonian, but the heavy ones remain non-Newtonian.

Localization and characterization of human papillomavirus-16 in oral squamous cell carcinoma.

OBJECTIVES: The role of Human papillomavirus (HPV) in the oral squamous cell carcinoma (OSCC) has not been completely elucidated. The purpose of the present study was to investigate the prevalence and localization of HPV-16 virus in OSCC and to correlate HPV-16 positivity and p16INK4A expression with the clinical and pathological features of OSCC. METHODS: The archives of Oral Pathology at the University of Florida, College of Dentistry were accessed for demographic, clinical, histopathological data, and slides of 114 OSCC patients. HPV-16 positivity of OSCC was evaluated by p16INK4A immunohistochemistry (IHC) and HPV-16 E6/E7mRNA by in situ hybridization (ISH). RESULTS: Out of 114 consecutive pathological slides of OSCC, 16 samples (14%) showed positivity for p16INK4A by IHC and 14 samples (12%) were positive for HPV-16 E6/E7mRNA ISH and the Positivity showed a significant correlation with the patients' age, alcohol consumption, and the degree of OSSC differentiation. The hard palate showed the highest positivity of p16INK4A IHC and HPV-16 mRNA ISH (38%, 36% respectively). CONCLUSION: HPV-16 is a significant factor in oral carcinogenesis. We recommend using p16INK4A as a surrogate marker for HPV detection in OSCC, which can be complemented by RNA ISH for the identification of HPV subtypes.

A lower prevalence of malignant lymphoma in Sjögren's syndrome patients: A cross-sectional study.

OBJECTIVE: This study aims to determine the prevalence and risk factors associated with lymphoma in primary Sjögren's syndrome (pSS). METHODS: We conducted a cross-sectional study on pSS patients who were registered into the Integrated Data Repository (IDR) at the University of Florida (UF) Health Shands Hospital. The parameters, such as age, sex, race, and smoking status, were included. Lymphoma types in pSS were categorized. The clinical and laboratory features were compared between pSS patients with and those without lymphoma by utilizing the items in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). RESULTS: Among 1,211,343 patients, we found 6799 patients (0.56%) with lymphomas and 2562 patients (0.21%) with pSS. Out of the 2562 pSS patients, 67 patients (2.6%) were diagnosed with lymphoma. The difference in the clinical and laboratory features listed under the ESSDAI domains between pSS patients with lymphomas and pSS without it was significant (p < 0.05 or 0.01): fever, weight loss, lymphadenopathy, splenomegaly, lacrimal gland diseases, cough, shortness of breath, hematuria, cerebrovascular accident diseases, peripheral nerve involvement due to vasculitis, neutropenia, and thrombocytopenia. CONCLUSION: We report 2.6% of lymphoma prevalence in pSS, lower than previously reported in the literature.

Increased Risk for Acute Periapical Abscesses in Multiple Sclerosis Patients and the Possible Association with Epstein-Barr Virus.

INTRODUCTION: Multiple sclerosis (MS) is a severe inflammatory neuroimmune degenerative condition affecting more than 2 million individuals worldwide. The purpose of this study was to assess the prevalence of acute periapical abscesses in patients with MS and to evaluate whether acute periapical abscesses (PAs) are more likely to affect patients who were previously infected by Epstein-Barr virus (EBV). METHODS: Integrated data of hospital patients were used. Data from the corresponding diagnosis codes for MS and acute PA were retrieved by querying the appropriate International Classification of Diseases, Tenth Revision codes in the database. RESULTS: Of the total hospital patient population, 0.18% were diagnosed with a history of MS. Females were more affected than males 3.25-fold. Whites were more affected than African Americans 6-fold. Whites were more affected than African Americans combined with other ethnicities 3.6-fold. The odds ratio (OR) for acute PAs in patients with a history of MS was 2.2 (P < .0001). After adjustment for diabetes mellitus comorbidity, the OR for acute PAs in patients with a history of MS was 2.6. After adjustment for cardiovascular disease comorbidity, the OR for acute PAs in patients with a history of MS was 1.27. Of the patients who presented with PAs, 0.2% were diagnosed with a history of EBV infection. The OR was 3.98, and the difference in prevalence was statistically significant (P < .0001). CONCLUSIONS: Under the conditions of this cross-sectional study, it appears that the prevalence of acute PAs is higher in patients with MS and that EBV may play a role.

Acute periapical abscesses in patients using selective serotonin reuptake inhibitors.

AIMS: Depression and anxiety are severe health problems affecting millions of individuals worldwide. Consequently, the use of antidepressants has constantly been on a rise. Selective serotonin reuptake inhibitors (SSRIs) antidepressant are now commonly used due to fewer side effects as compared to other types of antidepressants. The aim of this study was to assess the prevalence of periapical abscesses (PAs)in patients using SSRIs. METHODS AND RESULTS: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for SSRIs and acute PAs was retrieved by searching the appropriate query in the database. The different diagnoses were coded using the international coding systems ICD 10. Diagnosis was made by calibrated dentists in a hospital setting based on clinical examination and imaging data. The odds ratio (OR) for the prevalence of acute PAs and its association with the use of SSRIs were calculated and analyzed statistically. It was found that the prevalence of acute PAs was significantly higher in patients using SSRIs as compared to the other hospital patient population. The OR was 2.8 and the difference between patients using SSRIs and patients who do not was statistically significant (p < .0001). CONCLUSION: Under the conditions of this study, it appears that the prevalence of acute PAs is higher in patients using SSRIs.

Idiopathic lingual mandibular sequestration and its relationship to medication-related osteonecrosis of the jaws (MRONJ): mini review.

OBJECTIVE: Idiopathic lingual mandibular sequestration is an uncommon condition that affects the lingual aspect of the mandible and may result in a necrosis of the jaw that is clinically indistinguishable from medication-related osteonecrosis of the jaw. This condition, however, is not associated with the intake of antiresorptive medication and may not require the same safeguards for extended periods of time. The etiology of idiopathic lingual mandibular sequestration is still unknown although trauma has been shown to play an important role. METHOD AND MATERIALS: PubMed and the Cochrane Library were used to retrieve papers written in English through the years 1970 to 2021 using the key words "idiopathic osteonecrosis," "lingual sequestration," and "idiopathic jaw sequestration." In addition, clinical presentation of the lesion was included. RESULTS: Idiopathic lingual mandibular sequestration is a benign, mostly self-limiting condition distinct from medication- related osteonecrosis of the jaw. CONCLUSION: The dental clinician should be familiar with this condition and include it in their differential diagnosis when exposed bone is present with no history of radiation to the area or intake of antiresorptive medication. The course of the condition is usually very mild and may be self-limiting and usually does not require surgical intervention.

Medication-Related Osteonecrosis of the Jaw in Cancer Patients: Result from the OneFlorida Clinical Research Consortium.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severely debilitating drug-induced bone disorder in the jawbone region. The first MRONJ was reported in 2003 after bisphosphonate (BP) exposure. Recently, other drugs, such as receptor activator of NF-κB ligand (RANKL) inhibitor denosumab and antiangiogenic agents, were also associated with MRONJ. The purpose of this study was to evaluate the incidence and risk factors for MRONJ related to BPs or denosumab in cancer patients in real-world clinical settings using data from the OneFlorida Clinical Research Consortium. We queried the electronic health records of participants with prescriptions of intravenous (IV) BPs or denosumab between January 1, 2012, and September 1, 2021, in the OneFlorida Consortium. Time to MRONJ diagnosis was evaluated using the Kaplan-Meier method, and Cox regression analysis was performed to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for MRONJ. A total of 5689 participants had one or more prescriptions of IV BP or denosumab within this study period and were included in this study. Among these participants, 52 (0.9%) had a diagnosis of MRONJ. The overall rate of MRONJ was 0.73%, 0.86%, and 3.50% in the cancer patients treated with IV BPs, denosumab, and sequential IV BPs and denosumab, respectively. The risk of MRONJ was similar in participants treated with denosumab alone compared to those treated with IV BPs alone (HR: 1.25, 95% CI: 0.66-2.34, p = .49). Patients with sequential prescription of IV BP and denosumab were at much higher risk for MRONJ, with an adjusted HR of 4.49, 95% CI of 1.96-10.28, p = .0004. In conclusion, in real-world clinical settings, the rates of MRONJ associated with IV BPs and denosumab were similar, while the sequential treatment of these two drug classes was associated with a much higher risk of MRONJ. © 2022 American Society for Bone and Mineral Research (ASBMR).

Multiple oral squamous cell carcinoma 6 years after allogeneic stem cell transplantation complicated with chronic graft-versus-host disease: A case report.

Oral squamous cell carcinoma is a potential long-term complication after hematopoietic stem cell transplantation. This may be related to mechanisms including radiation and chemotherapy regimens, chronic graft-versus-host disease, inflammation, and prolonged immunosuppression. The current case describes the development of multiple oral white thick keratotic lesions in the floor of the mouth and the tongue 6 years after hematopoietic stem cell transplantation complicated with chronic graft-versus-host disease. A biopsy performed with histopathological analysis revealed a well-differentiated squamous cell carcinoma. The patient was treated by subtotal glossectomy, bilateral neck dissection, and flap reconstruction. This report highlights the significance of the routine oral examination of long-term surveillance post hematopoietic stem cell transplantation to ensure early detection of these tumors at potentially treatable stage.

Periapical disease in post-stroke patients.

PURPOSE: To assess the prevalence of acute periapical abscesses (PAs) in patients with history of stroke. METHODS: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for PAs and stroke were retrieved by searching the appropriate query in the database. The odds ratio (OR) of acute PAs and its association with post-stroke conditions was calculated and analyzed statistically. RESULTS: The prevalence of acute PAs in patients with stroke history was 1.39% as compared to 0.6% in the general patient population of the hospital. The OR was 2.78 and the difference was statistically significant (P< 0.0001). The prevalence of acute PAs in patients with a history of hemorrhagic stroke was 1.19% and the OR was 2.38. The difference was statistically significant (P< 0.0001). The prevalence of acute PAs in patients with a history of cerebral infarction was 1.55% and the OR was 3.11. The difference was statistically significant (P< 0.0001). The prevalence of acute PAs in patients with a history of cerebral infarction without hypertension was 0.87% and the OR was 1.75. The difference was statistically significant (P< 0.0001). CLINICAL SIGNIFICANCE: Oral healthcare providers should be aware of the possible higher prevalence of periapical abscesses in post-stroke patients. This can include patients with a history of hemorrhagic stroke or cerebral infarction.

Brain contrast-enhanced ultrasonography and elastography in infants.

Advanced ultrasound techniques, including brain contrast-enhanced ultrasonography and elastography, are increasingly being explored to better understand infant brain health. While conventional brain ultrasonography provides a convenient, noninvasive means of assessing major intracranial pathologies, its value in revealing functional and physiologic insights into the brain lags behind advanced imaging techniques such as magnetic resonance imaging. In this regard, contrast-enhanced ultrasonography provides highly precise functional information on macrovascular and microvascular perfusion, while brain elastography offers information on brain stiffness that may be associated with relevant physiological factors of diagnostic, therapeutic, and/or prognostic utility. This review details the technical background, current understanding and utility, and future directions of these two emerging advanced ultrasound techniques for neonatal brain applications.