Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3.

We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax > 6 s perfusion lesion predicts the infarct volume at 24 h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24 h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p = 0.006; CBV Index 0.78 vs. 0.85, p = 0.001) and 24 h (HIR 0.56 vs. 0.07, p = 0.004; CBV Index 0.47 vs. 0.73, p = 0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p = 0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24 h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24 h.

Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3.

Background and Purpose- Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods- We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results- Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P=0.17, Tmax >6 seconds 98 versus 100 mL; P=0.48) yet experienced less infarct growth (15 versus 59 mL; P<0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P<0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P<0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions- About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3.

Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Whole-cortical graphical networks at wakeful rest in young and older adults revealed by functional near-infrared spectroscopy.

A good understanding of age-dependent changes and modifications in brain networks is crucial for fully exploring the effects of aging on the human brain. Few reports have been found in studies of functional brain networks using functional near-infrared spectroscopy (fNIRS). Moreover, little is known about the feasibility of using fNIRS to assess age-related changes in brain connectomes. This study applied whole brain fNIRS measurement, combined with graph theory analysis, to assess the age-dependent changes in resting-state brain networks. Five to eight minutes of resting-state brain hemodynamic signals were recorded from 48 participants (18 young adults and 30 older adults) with 133 optical channels covering the majority of the cortical regions. Both local and global graph metrics were computed to identify the age-related changes of topographical brain networks. Older adults showed an overall decline of both global and local efficiency compared to young adults, as well as the decline of small-worldness. In addition, young adults showed the abundance of hubs in the prefrontal cortex, whereas older adults revealed the hub shifts to the sensorimotor cortex. These obvious shifts of hubs may potentially indicate decreases of the decision-making, memory, and other high-order functions as people age. Our results showed consistent findings with published literature and also demonstrated the feasibility of whole-head fNIRS measurements to assess age-dependent changes in resting-state brain networks.

Prefrontal hemodynamic mapping by functional near-infrared spectroscopy in response to thermal stimulations over three body sites.

Functional near-infrared spectroscopy (fNIRS) was used to examine hemodynamic responses in the prefrontal cortex (PFC) during noxious thermal pain, induced by thermal stimulations over three different body sites over the right forearm, right temporomandibular joint, and left forearm. Functional NIRS measurements were obtained from three groups of healthy volunteers, one group for each body region. Each group was subjected to both low-pain stimulation (LPS) and high-pain stimulation (HPS) by a [Formula: see text] thermode of a temperature-controlled thermal stimulator over the respective three body sites. Our results showed that HPS given at three sites induced significant increases ([Formula: see text]) in oxy-hemoglobin concentration ([Formula: see text]) in the PFC with similar temporal patterns in relatively spread PFC areas. In contrast, LPS did not cause any significant [Formula: see text] in the PFC of any subject group. Our observed PFC activations induced by acute HPS were generally consistent with previous reports by fMRI studies. The study also found a peculiar global trend of postpain deactivation in the PFC, which is attributed to global vasoconstriction due to acute nocuous pain. Overall, these results indicate that hemodynamic activities in PFC exhibit consistent temporal and spatial patterns in response to acute thermal stimulation given across all three body sites.

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy.

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported.

An fNIRS investigation of associative recognition in the prefrontal cortex with a rapid event-related design.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) measures hemodynamic changes at the cortical level. The use of fNIRS is growing in popularity for studying cognitive neuroscience in which event-related designs are widely used with functional magnetic resonance imaging (fMRI). However, the applicability of event-related designs with fNIRS has not been fully understood. Therefore, the present study employed fNIRS with a rapid-presentation event-related design for investigating prefrontal cortical activity during complex associative recognition. NEW METHOD: Participants studied a list of word pairs and were later given an associative recognition test. Throughout the experiment, each event was presented rapidly (∼4s). Data were sorted based on accuracy of associative memory judgments and analyzed using the general linear model (GLM) with an event-related design. RESULTS: During retrieval, significant increases in oxygenated hemoglobin concentrations were observed in dorsolateral and ventrolateral prefrontal regions for successful associative recognition. When comparing retrieval to encoding, significant increases in oxygenated hemoglobin concentrations were also observed in dorsolateral prefrontal cortex. COMPARISON WITH EXISTING METHOD: The current fNIRS results corroborate previous fMRI findings that have demonstrated the involvement of dorsolateral and ventrolateral prefrontal cortex in associative recognition. Therefore, the present study validates versatile use of fNIRS with a rapid-presentation event-related design in the investigation of neural mechanisms of associative memory. CONCLUSION: The findings of this study provide evidence that fNIRS can be a viable research method for investigating complex cognitive processes commonly of interest in cognitive neuroscience. Taken together, these results demonstrate that fNIRS can be a cost-effective and accessible experimental tool for cognitive neuroscience.

Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD): a functional near infrared spectroscopy study.

Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography.

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.