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Open Access Publications from the University of California

Scholarly Works (5 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2021)

Transcranial focused ultrasound stimulation (tUS) is an emerging technique for non-invasive brain stimulation (NIBS). tUS offers the option of higher spatial resolution and modulation of deeper neural structures, compared to other NIBS techniques. However, the neuromodulatory effects of tUS are still poorly understood, and the few experiments published thus far have shown variable outcomes between regions and studies.

To better understand the strengths, weakness, and feasibility prospects of tUS for use in humans, I compared tUS to an established NIBS technique, transcranial magnetic stimulation (TMS), in a cortical region with previously unclear tUS results but established TMS results: primary motor cortex (M1). I found no change in ongoing muscle activity concurrent with tUS stimulation. I also found no significant change in M1 cortical excitability due to tUS exposure.

To explore causes of variability in tUS, I performed acoustic simulations that replicated conditions of the M1 experiments. Specifically, I used participant-specific magnetic resonances images (MRI) to find where in the brain tUS pressure fields landed and how strong those pressure fields were. With this simulation data, I explored the spatial precision and volume of tUS, the accuracy of tUS device placement in my own data, and whether there was a correlation between tUS exposure and M1 excitability. I found that tUS produced a narrow ellipsoid intracranial pressure field with a full width at half maximum roughly 4 mm wide. While the simulations showed that tUS exposure levels varied, I found no clear correlation between tUS exposure and M1 excitability from these data.

Lastly, acoustic simulations provide significant insight for any tUS experiment, since it provides investigators estimates of the location and intensity of the intracranial ultrasonic field. However, implementing such simulations is challenging and time-consuming, which may explain why many published tUS studies do not perform acoustic simulations. To make acoustic simulation more accessible for tUS investigators, I built an open-source MATLAB toolbox that integrates medical imaging and neuronavigation with acoustic simulation. An increased adoption of acoustic simulation in tUS experiments should accelerate collective progress within the field.

    Cover page: Transcranial ultrasound stimulation: promises and challenges
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2014)

    Objectives

    Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls.

    Methods

    Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns.

    Results

    There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008).

    Conclusions

    Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.
      Cover page: Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2014)
      Prenatal heart disease spans the spectrum of severity from very mild to severe life-threatening conditions. An accepted scale for grading fetal cardiovascular disease severity would aid in anomaly standardization, counseling, and future research. The Fetal
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2020)
        Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio [OR], 2.3 [1.1-5.0], 95% CI, per m/s; P=0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 [1.3-14.2]; P=0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.
          Cover page: Risk Factors for Mortality and Circulatory Outcome Among Neonates Prenatally Diagnosed With Ebstein Anomaly or Tricuspid Valve Dysplasia: A Multicenter Study
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2015)

          Background

          Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era.

          Methods and results

          Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001).

          Conclusion

          In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival.
            Cover page: Outcomes and Predictors of Perinatal Mortality in Fetuses With Ebstein Anomaly or Tricuspid Valve Dysplasia in the Current Era
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