Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD).

BACKGROUND: Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated. METHODS: We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children's hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit. CONCLUSIONS: This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03518216.

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes.

BACKGROUND AND PURPOSE: Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP). METHODS: We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome. RESULTS: A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome. CONCLUSIONS: Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.

The Role of CT Perfusion in Defining the Clinically Relevant Core Infarction to Guide Thrombectomy Selection in Patients with Acute Stroke.

BACKGROUND AND PURPOSE: Infarct core assessment on presentation is important to evaluate salvageable tissue to select patients for thrombectomy. Our study aims to evaluate the correlation between infarct core volume measured by computed tomography (CT) perfusion (CTP) and magnetic resonance diffusion-weighted imaging (MR-DWI) in patients with acute large-vessel occlusion. METHODS: We studied patients who underwent CTP on presentation to the emergency department for stroke symptoms. National Institute of Health Stroke Scale (NIHSS), collateral status, symptomatic vessels, and modified Rankin scale (mRS) at 90 days were collected. Admission infarct core volume was measured on initial relative cerebral blood volume and final infarct core volume on follow-up DWI. The correlation between two measures was assessed using Pearson's correlation coefficient. RESULTS: Seventy-four patients were studied of which 41.9% were female. Median NIHSS was 13 (2-30). Middle cerebral artery occlusion was present in 53 (71.6%) patients and 54 (72.9%) had good collaterals. Good functional outcome of mRS 0-2 was achieved by 60.8% at 90 days. There was a strong correlation between CTP and MR-DWI (r = .94). There was no significant difference between volume (in milliliters) on CTP (54.1 ± 69.8) and volume on DWI (50.3 ± 59.7; P = .18) using the paired t-test. CONCLUSION: CTP provides a good estimation of the core infarct volume. It performs well within the clinically relevant thresholds for patient selection for thrombectomy.

An approach to comparing accuracies of two FLAIR MR sequences in the detection of multiple sclerosis lesions in the brain in the absence of gold standard.

RATIONALE AND OBJECTIVES: The purpose of this study was to present a new methodology to compare accuracies of two imaging fluid attenuated inversion recovery (FLAIR) magnetic resonance sequences in detection of multiple sclerosis (MS) lesions in the brain in the absence of ground truth, and to determine whether the two sequences, which differed only in echo time (TE), have the same accuracy. MATERIALS AND METHODS: We acquired FLAIR images at TE(1) = 90 ms and TE(2) = 155 ms from 46 patients with MS (24-69 years old, mean 45.8, 15 males) and 11 healthy volunteers (23-54 years old, mean 37.1, 6 males). Seven experienced neuroradiologists segmented lesions manually on randomly presented corresponding TE(1) and TE(2) images. For every image pair, a "surrogate ground truth" for each TE was generated by applying probability thresholds, ranging from 0.3 to 0.5, to the weighted average of experts' segmentations. Jackknife alternative free-response receiver operating characteristic analysis was used to compare experts' performance on TE(1) and TE(2) images, using successively the TE(1)- and TE(2)-based ground truths. RESULTS: Supratentorially, there were significant differences in relative accuracy between the two sequences, ranging from 8.4% to 12.1%. In addition, we found a higher ratio of false positives to true positives for the TE(2) sequence using the TE(2) ground truth, compared to the TE(1) equivalent. Infratentorially, differences in the relative accuracy did not reach statistical significance. CONCLUSION: The presented methodology may be useful in assessing the value of new clinical imaging protocols or techniques in the context of replacing existing ones, when the absolute ground truth is not available, and in determining changes in disease progression in follow-up studies. Our results suggest that the sequence with shorter TE should be preferred because it generates relatively fewer false positives. The finding is consistent with results of previous computer simulation studies.

Simultaneous assessment of motor and language areas with a single functional MR imaging paradigm: feasibility.

The purpose of this study was to test a hybrid multitask paradigm in healthy subjects and in a patient at preoperative functional magnetic resonance (MR) imaging. In this new paradigm, tasks related to different centers of brain function (motor and language) are performed in alternation during a single functional MR imaging examination, without the typical rest period, to improve time efficiency without compromising the quality of activation maps. The institutional review board approved the study, and all participants gave informed prior consent. The study complied with the Health Insurance Portability and Accountability Act. Seven healthy right-handed volunteers (four men, three women; age range, 22-40 years) were studied first. In both individual and group analyses, there was no statistically significant difference in results between assessment with the multitask design and that with the traditional block design. An advantage of the new paradigm was substantial time savings because the subject was engaged during the entire examination. Finally, the multitask design was tested in a patient undergoing preoperative evaluation, with similar results; therefore, use of the multitask design is feasible in a clinical setting.

On the use of caffeine as a contrast booster for BOLD fMRI studies.

This study explored the possible use of caffeine as an agent to improve the BOLD (blood oxygen level-dependent) signal response in fMRI. Previous research has demonstrated that caffeine has the ability to reset the level of coupling between blood flow and neuronal activity. In the present study, it has been shown that caffeine causes a decrease in cerebral perfusion by as much as 13.2% without a change in performance. Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4.4%. During activation, the vasculature responds from below-normal baseline levels with a normal increase in blood flow and volume, resulting in an overall increase in the BOLD contrast. This increase can be as large as 22-37% during the performance of a visually cued motor task. The benefit of such a large increase in the BOLD contrast could be used to improve the image resolution, the acquisition scheme, or the task design of fMRI experiments. Caffeine has the potential to be used as a contrast booster for fMRI experiments.