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Background: Radiation therapy is an integral component of treatment that can predispose to carotid artery stenosis (CAS) and increase the risk of cerebrovascular events for head and neck cancer survivors. The utility of screening for CAS with carotid ultrasound in asymptomatic head and neck cancer survivors is unclear. Methods: In this prospective, cross-sectional pilot study, 60 patients who have no evidence of cancer at least 2 years from completion of RT will undergo screening carotid ultrasound to identify patients with high risk of cardiovascular events. Results: Outcomes will include clinically significant CAS, carotid intima-media thickness, acceptability/feasibility of screening, barriers to care and preliminary data on changes to medical management because of screening. Correlative multi-omics analyses will examine biomarkers of CAS after radiation therapy. Conclusion: The results of this study will provide valuable data on the prevalence of CAS and preliminary patient-centered data that will inform the design of a future large-scale, multi-site clinical trial. Clinical Trial Registration:NCT05490875 (ClinicalTrials.gov) Plain Language Summary Patients with head and neck cancer are often treated with radiation therapy. Radiation therapy can cause damage to the blood vessels in the neck. This damage can manifest as narrowing of the blood vessels like the carotid artery, which can lead to stroke. Currently, it is not clear if screening head and neck cancer survivors with ultrasound scans of the carotid arteries is feasible or acceptable to patients. This has also not been formally assessed using a prospective clinical trial. In this study, patients with a history of head and neck cancer who have no evidence of their cancer for at least 2 years since completion of their radiation therapy will be enrolled. They will undergo blood testing and a research ultrasound of the carotid arteries to check for narrowing and other findings that may signal a high risk of stroke or another cardiovascular event. Participants will complete surveys on their experience with the process and how likely they are to accept further screening or additional treatment if something is found. They will also complete surveys on their perception of their personal risk of stroke and barriers to care that would prevent them from getting screening ultrasounds. Patients will be followed for up to 6 months after the ultrasound to check for any changes in their medical care that occurred because of the screening ultrasound. Article highlights Carotid artery stenosis in head & neck cancer survivors treated with radiation therapy Radiotherapy for head and neck (HN) cancer may increase the risk of accelerated atherosclerosis and late carotid artery stenosis (CAS) in 25% of patients, and screening of asymptomatic stenosis may be useful and cost-effective in specific high-risk populations. If clinically significant stenosis is identified, risk reduction strategies such as optimal medical management with or without procedural intervention may reduce the risk of stroke. Data supporting the use of carotid ultrasound (CUS) for HN cancer survivors are sparse, and no guideline currently recommends CUS screening for asymptomatic patients. Carotid ultrasound surveillance for detection of asymptomatic carotid artery stenosis after head & neck radiotherapy CUS allows for cardiovascular risk stratification using stenosis and intima-media thickness measurements. Knowledge gaps with regard to the use of CUS screening in this population include patient acceptability, feasibility, and clinical utility. Rates of change in medical management for screen-detected carotid stenosis in HN cancer survivors have not been assessed in a prospective study. Pilot trial of carotid artery ultrasound in head & neck cancer survivors In this single-institution trial, 60 patients with a history of HN cancer treated with radiotherapy will undergo screening CUS. Patients will be evaluated for CAS (peak systolic velocity by Doppler ultrasonography), and intima-media thickness will be measured. Outcomes include patient acceptability, feasibility, barriers to care and perceived stroke risk among participants. In patients with clinically significant stenosis, the rate of resultant medical interventions (e.g., new medication, additional imaging or intervention) will be determined. Conclusion This prospective study for CUS screening in HN cancer survivors will obtain novel preliminary data to better understand the utility and feasibility of a CUS screening program. Preliminary results will inform future trials focused on the efficacy and cost-effectiveness of carotid artery ultrasound screening in this patient population. Correlative analysis will elucidate novel biomarkers and mechanisms of post-radiotherapy CAS. [ABSTRACT FROM AUTHOR]

Objective: Effective interventions are needed to address postconcussive symptoms. We report the results of randomized, sham‐controlled trial of Cereset Research™ Standard Operating Procedures (CR‐SOP), a noninvasive, closed‐loop, allostatic, acoustic stimulation neurotechnology previously shown to improve insomnia. Methods: Military service members, veterans, or their spouses with persistent symptoms (Neurobehavioral Symptom Inventory [NSI] Score ≥23) after mTBI 3 months to 10 years ago, were randomized to receive 10 sessions of engineered tones linked to brainwaves (LB, intervention), or random engineered tones not linked to brainwaves (NL, sham control). The primary outcome was change in NSI, with secondary outcomes of heart rate variability and self‐report measures of sleep, mood, and anxiety. Results: Participants (n = 106, 22% female, mean age 37.1, 2.8 deployments, 3.8 TBIs) were randomized 1:1 to LB or NL, with no significant differences between groups at baseline. Among all study participants, the NSI declined from baseline 41.0 to 27.2 after (P < 0.0001), with gains largely sustained at 3 months (31.2) and 6 months (28.4). However, there were no significant differences between the LB (NSI declined from 39.9 at baseline to 28.2 post‐intervention, 31.5 at 3 months, and 29.4 at 6 months) and NL (NSI declined from 41.5 at baseline to 26.2, 29.9, and 27.3, respectively. Similar patterns were observed for the PCL5 and PHQ‐9 and there was no difference in HRV between groups. Interpretation: Ten hours of acoustic stimulation while resting in a zero‐gravity chair improves postconcussive symptoms. However, linking tones to brain electrical activity did not reduce symptoms more than random tones. Registration: ClinicalTrials.gov – NCT03649958 [ABSTRACT FROM AUTHOR]

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1552-6569.2006.00053.x Byline: Pornpatr Ausavarungnirun (1), Hernan Sabio (1), Jongyeol Kim (1), Charles H. Tegeler (1) Keywords: Anemia; transcranial Doppler; dynamic vascular analysis Abstract: ABSTRACT Background. By the age of 20 years, 10% of sickle cell disease (SCD) patients have experienced a stroke. It is unclear if SCD stroke is due primarily to hemodynamic effects of intracranial stenosis, or metabolic failure from anemia. Transcranial Doppler ultrasound (TCD) identifies a SCD subgroup with high stroke risk, but high mean flow velocity (MFV) can be due to stenosis or high flow rate, as with metabolic hyperemia of severe anemia. Dynamic Vascular Analysis (DVA; New Health Sciences, Inc., Bethesda, MD) is a new way to analyze TCD data, with potential to separate structural from metabolic causes of high MFV. Methods. Eighty SCD patients, regardless of hemoglobin genotypes, aged 2 to 22 years, without clinical stroke or transient ischemic attack (TIA), who had TCD (1/1/02 to 1/1/04) as part of routine outpatient clinical follow-up, with both the TCD report and study videotape available, were included. Waveforms were reviewed and marked by protocol, and DVA indices calculated including MFV, pulsatility index (PI), systolic acceleration (SA), dynamic flow index (DFI), dynamic pressure index (DPI), and dynamic compliance index (DCI). Mean and standard deviation were defined for the whole group, and for four subgroups, by age. Results. MFV, DFI, and DPI were highest at 6- to 9-year-olds, declining thereafter. The 14- to 22-year-old group was also compared to a group of healthy young athletes (15- to 22 years old). SCD patients had higher MFV, lnSA, DFI, DPI, and lower PI and DCI in most segments, suggesting global hyperemia. Conclusion. This is the first report of cross-sectional results of DVA in a cohort of SCD outpatients without prior clinical stroke (TIA). These results suggest hyperemia without significant focal intracranial stenosis. There were also differences between asymptomatic SCD and young athletes, and the MFV, DFI, and DPI were highest at the age of 6 to 9 years, decreasing as age increased. Author Affiliation: (1)From the Division of Neurology, Faculty of Medicine, Thammasat University (PA); Department of Neurology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC (PA, JK, TCH); Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC (HS). Article History: Received April 6, 2005, and in revised form November 10, 2005. Accepted June 6, 2006. Article note: Address correspondence to Charles H. Tegeler, MD, Department of Neurology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1078, USA. E-mail: ctegeler@wfubmc.edu.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1552-6569.2006.00044.x Byline: Ulf Schminke (1), Lillian Motsch (1), Li-Ming Lien (1), Teng-Yeow Tan (1), M. Gene Bond (1), James F. Toole (1), Charles H. Tegeler (1) Keywords: Screening; ultrasonography; power Doppler imaging; carotid artery stenosis Abstract: ABSTRACT Background and Purpose. We investigated the diagnostic performance of a brief Power Doppler Imaging (PDI) screening examination for carotid artery stenoses using a newly developed portable instrument. Methods. A highly experienced sonographer screened in total 152 carotid arteries by either continuous wave (cw) Doppler (n= 50) or a lightweight (2.4 kg) portable duplex device (n= 102) in a prospective study of 76 high-risk patients. The screening protocols included either spectrum analysis and frequency shift measurement in both internal carotid arteries with cw-Doppler or determination of area and diameter ratios in transverse and longitudinal views of both carotid arteries in B-mode and with PDI, but without velocity measurement. Both protocols were evaluated against a complete routine duplex ultrasonography examination. Results. According to the complete examination, stenoses were Conclusions. The diagnostic performance of the cw-Doppler protocol was superior to the PDI protocol. Nevertheless, both protocols appear suitable as inexpensive screening strategies to identify subjects with >75% stenosis measured by carotid Doppler ultrasound. However, these preliminary data need further verification. Author Affiliation: (1)From the Department of Neurology, Wake Forest University Baptist Medical Center, Winston-Salem, USA (US, LM, L-ML, T-YT, JFT, CHT); Division of Vascular Ultrasound Research, Department of Neurobiology and Anatomy, Wake Forest University Baptist Medical Center, Winston-Salem, USA (MGB); Department of Neurology, Ernst Moritz Arndt University, Greifswald, Germany (US, LM); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (L-ML); and Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan (T-YT). Article History: Received December 14, 2004, and in revised form August 10, 2005, December 8, 2005 and March 13, 2006. Accepted for publication March 16, 2006. Article note: Address correspondence to Ulf Schminke, MD, Department of Neurology, Sigmaringen Hospital, Hohenzollernstrasse 40, D-72488 Sigmaringen, Germany. E-mail: u.schminke@klksig.de, UlfSchminke@aol.com.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1177/1051228405001523 Byline: Pornpatr Likittanasombut (1), Patrick Reynolds (1), Dana Meads (1), Charles Tegeler (1) Keywords: Ultrasound; Volume flow rate; Catatid stenosis Abstract: ABSTRACT Background. Common carotid artery (CCA) volume flow rate (VFR) is clinically useful for study of cerebrovascular disease. Color Velocity Imaging Quantification (CVI-Q; Philips Ultrasound International, Irvine, CA), previously reported as accurate and reliable, tracks the flow lumen over the cardiac cycle, as well as mean spatial velocity, which is multiplied by vessel area to obtain VFR. VFR can also be obtained by Doppler sampling for mean velocity, and vessel area based on static B-mode lumen diameter. We compared CCA VFR by CVI-Q and Doppler method (DM), since knowledge of how they compare is crucial when both are used clinically. Method. We prospectively studied patients having clinical carotid duplex exams and healthy controls. All had CCA VFR measured by both methods in the same exam session. Results. Thirty-four studies were reviewed. CCA VFR by CVI-Q in those without ICA stenosis was 337 [+ or -] 96 mL/m, and by DM 359 [+ or -] 130 mL/m; P= .33. There was no difference between methods for 50-75% or 75-95% ICA stenosis. In 7 patients with ICA occlusion, and 3 with 95-99% stenosis, VFR was higher by DM than by CVI-Q (Occlusion: 125 vs 58 mL/m, P= .007; 95-99%: 152 vs 63 mL/m, P= .038). There was no statistically significant difference between methods for measurement of the ratio of VFR between right and left CCA. Conclusion. In patients with 0-95% ICA stenosis, VFR by CVI-Q and DM showed no difference. For 95-100% ICA stenosis the methods differ; with higher VFR by DM. Side-to-side VFR ratios remain constant, irrespective of VFR method, and can still provide clinically useful information. Author Affiliation: (1)From the Department of Neurology, Department of Medicine, Faculty of Medicine, Thammasat University, Patumthani, Thailand and the Department of Neurology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina. Article History: Received November 1, 2004, and in revised form June 27, 2005. Accepted for publication August 4, 2005. Article note: Address correspondence to Charles Tegeler, MD, Department of Neurology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1078. E-mail: ctegeler@wfubmc.edu.