Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans: a pharmacological study.

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.

Intracerebral Hemorrhage Segmentation on Noncontrast Computed Tomography Using a Masked Loss Function U-Net Approach.

OBJECTIVE: Intracerebral hemorrhage (ICH) volume is a strong predictor of outcome in patients presenting with acute hemorrhagic stroke. It is necessary to segment the hematoma for ICH volume estimation and for computerized extraction of features, such as spot sign, texture parameters, or extravasated iodine content at dual-energy computed tomography. Manual and semiautomatic segmentation methods to delineate the hematoma are tedious, user dependent, and require trained personnel. This article presents a convolutional neural network to automatically delineate ICH from noncontrast computed tomography scans of the head. METHODS: A model combining a U-Net architecture with a masked loss function was trained on standard noncontrast computed tomography images that were down sampled to 256 × 256 size. Data augmentation was applied to prevent overfitting, and the loss score was calculated using the soft Dice loss function. The Dice coefficient and the Hausdorff distance were computed to quantitatively evaluate the segmentation performance of the model, together with the sensitivity and specificity to determine the ICH detection accuracy. RESULTS: The results demonstrate a median Dice coefficient of 75.9% and Hausdorff distance of 2.65 pixels in segmentation performance, with a detection sensitivity of 77.0% and specificity of 96.2%. CONCLUSIONS: The proposed masked loss U-Net is accurate in the automatic segmentation of ICH. Future research should focus on increasing the detection sensitivity of the model and comparing its performance with other model architectures.

The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

OBJECTIVE: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion. METHODS: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. RESULTS: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76). CONCLUSIONS: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications.

Cerebrovascular Neuroprotection after Acute Concussion in Adolescents.

OBJECTIVE: To assess acute cerebrovascular function in concussed adolescents (14-21 years of age), whether it is related to resting cerebral hemodynamics, and whether it recovers chronically. METHODS: Cerebral vasoreactivity and autoregulation, based on middle cerebral artery blood flow velocity, was assessed in 28 concussed participants (≤14 days of injury) and 29 matched controls. The participants in the concussion group returned for an 8-week follow-up assessment. Over the course of those 8-weeks, participants recorded aerobic exercise frequency and duration. RESULTS: Between groups, demographic, clinical, and hemodynamic variables were not significantly different. Vasoreactivity was significantly higher in the concussed group (p = 0.02). Within the concussed group, 60% of the variability in resting cerebral blood flow velocity was explained by vasoreactivity and two components of autoregulation - falling slope and effectiveness of autoregulation (adjusted R2  = 0.60, p < 0.001). Moreover, lower mean arterial pressure, lower responses to increases in arterial pressure, and lower vasoreactivity were significantly associated with larger symptom burden (adjusted R2  = 0.72, p < 0.01). By the 8-week timepoint, symptom burden, but not vasoreactivity, improved in all but four concussed participants (p < 0.01). 8-week change in vasoreactivity was positively associated with aerobic exercise volume (adjusted R2  = 0.19, p = 0.02). INTERPRETATION: Concussion resulted in changes in cerebrovascular regulatory mechanisms, which in turn explained the variability in resting cerebral blood flow velocity and acute symptom burden. Furthermore, these alterations persisted chronically despite symptom resolution, but was positively modified by aerobic exercise volume. These findings provide a mechanistic framework for further investigation into underlying cerebrovascular related symptomatology. ANN NEUROL 2021;90:43-51.

Intracranial Blood Flow Quantification by Accelerated Dual-venc 4D Flow MRI: Comparison With Transcranial Doppler Ultrasound.

BACKGROUND: Dual-venc 4D flow MRI, recently introduced for the assessment of intracranial hemodynamics, may provide a promising complementary approach to well-established tools such as transcranial Doppler ultrasound (TCD) and overcome some of their disadvantages. However, data comparing intracranial flow measures from dual-venc 4D flow MRI and TCD are lacking. PURPOSE: To compare cerebral blood flow velocity measures derived from dual-venc 4D flow MRI and TCD. STUDY TYPE: Prospective cohort. SUBJECTS: A total of 25 healthy participants (56 ± 4 years old, 44% female). FIELD STRENGTH/SEQUENCE: A 3 T/dual-venc 4D flow MRI using a time-resolved three-dimensional phase-contrast sequence with three-dimensional velocity encoding. ASSESSMENT: Peak velocity measurements in bilateral middle cerebral arteries (MCA) were quantified from dual-venc 4D flow MRI and TCD. The MRI data were quantified by two independent observers (S.M and Y.M.) and TCD was performed by a trained technician (A.L.M.). We assessed the agreement between 4D flow MRI and TCD measures, and the interobserver agreement of 4D flow MRI measurements. STATISTICAL TESTS: Peak velocity from MRI and TCD was compared using Bland-Altman analysis and coefficient of variance. Intraclass correlation coefficient (ICC) was used to assess MRI interobserver agreement. A P value < 0.05 was considered statistically significant. RESULTS: There was excellent interobserver agreement in dual-venc 4D flow MRI-based measurements of peak velocity in bilateral MCA (ICC = 0.97 and 0.96 for the left and right MCA, respectively). Dual-venc 4D flow MRI significantly underestimated peak velocity in the left and right MCA compared to TCD (bias = 0.13 [0.59, -0.33] m/sec and 0.15 [0.47, -0.17] m/sec, respectively). The coefficient of variance between dual-venc 4D flow MRI and TCD measurements was 26% for the left MCA and 22% for the right MCA. DATA CONCLUSION: There was excellent interobserver agreement for the assessment of MCA peak velocity using dual-venc 4D flow MRI, and ≤20% under-estimation compared with TCD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Predictors of Acute Transfer and Mortality Within 6 Months From Admission to an Inpatient Rehabilitation Facility for Patients With Brain Tumors.

OBJECTIVE: To obtain useful information for clinicians in evaluating patients with brain tumors for transfer to and subsequent care in inpatient rehabilitation facilities (IRFs). DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: A total of 208 adults with either initial or recurrent brain tumors who were admitted to an IRF between January 2017 and December 2018 after an acute hospitalization. INTERVENTIONS: None MAIN OUTCOME MEASURES: Transfer from an IRF to an acute care hospital and mortality within 6 months from admission to an IRF. RESULTS: Of the 208 patients who met inclusion criteria, 20.2% were transferred to an acute care hospital during the IRF stay, which was associated with prior chemotherapy, steroid use, and laterality of tumor. In total, 36.9% of patients with brain tumors died within 6 months of an IRF admission that was associated with recurrent tumor diagnosis, prior chemotherapy, prior neurosurgical intervention, prior neurostimulant use, use of steroids, isocitrate dehydrogenase and O6-methyl-guanyl-methyl-transferase biomarkers, and laterality and location of tumor. CONCLUSIONS: Patients with brain tumors have a notable potential for acute hospital transfer and mortality within 6 months of IRF stay, with several tumor- and treatment-related risk factors. This information can help identify functional goals, identify high risk patients, enable closer clinical monitoring, and facilitate focused care discussions at IRFs.

"All-in-one" window/level whole-body computed tomography scan - A faster way to evaluate trauma cases.

PURPOSE: To investigate the accuracy and total assessment time (TAT) of the "All-in-one" (AIO)-window/level setting for whole-body computed tomography (CT) image compared to multiple tissue-specific window/level settings conventionally used for detection of traumatic injuries. METHOD: Contrast-enhanced chest, abdomen, and pelvic CT scans of 50 patients who presented to our emergency department (ED) for major trauma were retrospectively selected. In a simulation of a "wet read" performed at the CT scanner console, 6 readers with different levels of experience had up to 3 min to describe any traumatic finding identified on the CTs. The readers reviewed each patient in two different sessions separated by a washout period to suppress any recall bias from one session to the next. Each scan was reviewed once using the AIO-window/level setting and another time using the conventional bone, lung, and soft tissue window/level display settings, in a randomized order. The CT reports were used as reference standard. RESULTS: Overall, there was no statistically significant difference in the assessment accuracy of the review based on the AIO or the conventional window/level settings (0.89 ± 0.09 vs 0.90 ± 0.08). Using the AIO-window/level settings, TAT was 14.3 s faster when compared with the conventional window/level settings (2.33 ± 0.63 vs 2.57 ± 0.51 min; p < 0.001). CONCLUSIONS: In a time-delimited image review, similar diagnostic accuracy was reached faster using the AIO vs the conventional window/level settings. When providing a "wet read" at the CT console, the ability to identify traumatic injury using a single AIO-window/level may help expedite patient management.

Postconcussion Exercise Volume Associations With Depression, Anxiety, and Dizziness Symptoms, and Postural Stability: Preliminary Findings.

OBJECTIVE: To examine the association between postconcussion exercise volume and changes in depression, anxiety, dizziness, and postural stability. DESIGN: Secondary analysis of a single-site prospective clinical trial. SETTING: Cerebrovascular research laboratory. PARTICIPANTS: Participants completed questionnaires and underwent tests of gait and balance within 2 weeks of a concussion (mean = 11 ± 3 days postconcussion) and approximately 1 month later (mean = 41 ± 7 days postconcussion). Exercise volume was tracked by weekly exercise logs. INTERVENTIONS: On the basis of a previous work classifying exercise volume following concussion, we grouped participants according to self-reported exercise volume between visits as high exercise volume (≥150 min/wk) or low exercise volume (<150 min/wk). MAIN OUTCOME MEASURES: Participants completed assessments evaluating anxiety and depression (Hospital Anxiety and Depression Scale), dizziness (Dizziness Handicap Inventory), and postural stability (tandem gait and modified Balance Error Scoring System). RESULTS: Thirty-eight participants completed the study, of which 22 were in the high exercise volume group (mean = 71 ± 40 min/wk; 16.8 ± 2.1 years; 59% female) and 16 were in the low exercise volume group (mean = 379 ± 187 min/wk; 17.5 ± 2.1 years; 31% female). Although depression symptoms were not significantly different initially (mean difference = 1.5; 95% CI, -0.68 to 3.68; P = .24), the high exercise volume group had significantly lower depression symptom scores at follow-up (mean difference = 3.0; 95% CI, 1.40 to 4.47; P < .001). Anxiety symptoms (mean difference = 2.8; 95% CI, 0.3 to 5.4; P = 0.03), dizziness symptoms (mean difference = 10.9; 95% CI, 0.2 to 21.5; P = .047), single-task tandem gait (mean difference = 3.1 seconds; 95% CI, 0.2 to 6.0; P = .04), and dual-task tandem gait (mean difference = 4.2 seconds; 95% CI, 0.2 to 8.2; P = .04) were significantly better among the high exercise volume group. CONCLUSION: Greater exercise volumes were associated with lower depression, anxiety, and dizziness symptoms, and faster tandem gait performance. These preliminary findings suggest a potentially beneficial role for exercise within several different domains commonly affected by concussion.

Clazosentan for Improvement of Time to Peak Perfusion in Patients with Angiographically Confirmed Severe Vasospasm.

BACKGROUND: Clazosentan, an endothelin-1 receptor antagonist, has been shown to prevent the development of large vessel angiographic vasospasm after aneurysmal subarachnoid hemorrhage. We hypothesized that clazosentan can improve cerebral perfusion for territories affected by angiographically confirmed vasospasm. METHODS: The REVERSE study (REversal of Vasospasm with clazosEntan post-aneuRysmal Subarachnoid hEmorrhage) was a prospective multicenter open-label pilot study of adult patients with aneurysmal subarachnoid hemorrhage who received intravenous clazosentan after developing moderate to severe angiographic vasospasm. Using the radiographic data from the REVERSE study and additional retrospective radiographic data from our tertiary medical center, we compared the impact of intravenous clazosentan with intraarterial vasodilator therapy (medical standard of care) on vasospasm reversal using time to peak perfusion (TTPP; the time interval between the peak opacification of contrast dye in the main artery supplying an anatomically defined territory and the parenchymal phase when the dye is diffusely present in the brain parenchyma). RESULTS: Both intravenous clazosentan (n = 7 vessels) and intraarterial vasodilator therapy (n = 11 vessels) resulted in a statistically significant improvement in TTPP at 24 h post intervention, when compared with the TTPP just prior to intervention for territories with angiographically confirmed severe vasospasm in the proximal arteries at baseline (linear mixed-effect model, p = 0.02). The clazosentan and intraarterial vasodilator therapy groups exhibited no statistically significant interaction term [time x treatment group (medical standard of care vs. clazosentan)] in our model (p = 0.71), suggesting similar temporal course of two therapies. CONCLUSIONS: In our small pilot study, intravenous clazosentan administered for at least 24 h had an effect comparable with that of intraarterial vasodilator therapy in reversing angiographically confirmed severe vasospasm. Our results may indicate that clazosentan, in an appropriately selected patient cohort, could offer a noninvasive approach for alleviating vasospasm.

Dizziness, Psychosocial Function, and Postural Stability Following Sport-Related Concussion.

OBJECTIVE: To examine if self-reported dizziness is associated with concussion symptoms, depression and/or anxiety symptoms, or gait performance within 2 weeks of postconcussion. DESIGN: Cross-sectional study. SETTING: Research laboratory. PARTICIPANTS: Participants were diagnosed with a concussion within 14 days of initial testing (N = 40). Participants were divided into 2 groups based on their Dizziness Handicap Inventory (DHI) score: 36 to 100 = moderate/severe dizziness and 0 to 35 = mild/no dizziness. INTERVENTIONS: Participants were tested on a single occasion and completed the DHI, hospital anxiety and depression scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Post-Concussion Symptom Inventory (PCSI). Three different postural control tests were use: modified Balance Error Scoring System, single-/dual-task tandem gait, and a single-/dual-task instrumented steady-state gait analysis. MAIN OUTCOME MEASURES: Comparison of patient-reported outcomes and postural control outcomes between moderate/severe (DHI ≥ 36) and mild/no (DHI < 36) dizziness groups. RESULTS: Participants with moderate/severe dizziness (n = 19; age = 17.1 ± 2.4 years; 63% female) reported significantly higher symptom burden (PSCI: 43.0 ± 20.6 vs 22.8 ± 15.7; P = 0.001) and had higher median HADS anxiety (6 vs 2; P < 0.001) and depression (6 vs 1; P = 0.001) symptom severity than those with no/minimal dizziness (n = 21; age = 16.5 ± 1.9; 38% female). During steady-state gait, moderate/severe dizziness group walked with significantly slower single-task cadence (mean difference = 4.8 steps/minute; 95% confidence interval = 0.8, 8.8; P = 0.02) and dual-task cadence (mean difference = 7.4 steps/minute; 95% confidence interval = 0.7, 14.0; P = 0.04) than no/mild dizziness group. CONCLUSION: Participants who reported moderate/severe dizziness reported higher concussion symptom burden, higher anxiety scores, and higher depression scores than those with no/mild dizziness. Cadence during gait was also associated with the level of dizziness reported.

Similar Functional Gains Using Radial Versus Combined Shockwave Therapy in Management of Plantar Fasciitis.

Plantar fasciitis is a common condition that causes foot pain. While shockwave therapy has been shown to provide successful results, comparative outcomes from different forms of shockwave therapy have yet to be described for this condition. In this retrospective cohort study, we describe findings from a quality improvement initiative assessing safety and functional outcomes for patients with plantar fasciitis treated with radial shockwave therapy (n = 20) or radial and focused shockwave therapy (combined shockwave, n = 18). Most were runners (n = 31, 81.6%), mean age was 43.3 ± 12.9 years, and average symptom duration 12.1 ± 11.1 months. All patients were prescribed an exercise program focusing on foot intrinsic strengthening. We hypothesized both groups would have improvement in function using the foot and Ankle Ability Measure, with a similar safety profile. Both radial and combined groups received similar number of total treatments (4.9 ± 2.5 and 4.1 ± 2.4, respectively; p = .33). Within group score changes for the Activities of Daily Living and Sports subscales were observed for both the radial (16.5 ± 16.3, p < .001; 31.7 ± 23.1, p < .001) and combined groups (19.8 ± 10.8, p = .001; 26.0 ± 21.5, p = .003). There was no difference in proportion of patients meeting the minimal clinically important difference between radial and combined groups regarding the Activities of Daily Living (14 (70%) vs 14 (77.8%), p = .58) and Sports subscales (17 (85%) vs 12 (75%), p = .45). Collectively, these findings suggest that a majority of patients with chronic plantar fasciitis may achieve functional gains using either form of shockwave therapy.

Microemboli After Successful Thrombectomy Do Not Affect Outcome but Predict New Embolic Events.

Background and Purpose- We aimed to determine if microemboli after endovascular thrombectomy correlate with unfavorable outcomes despite successful recanalization. Methods- This is a prospective multicenter study of consecutive patients with ischemic stroke and occlusion of anterior circulation vessels (terminal internal carotid or main trunk of the middle cerebral artery/first-order branch of the main trunk of the middle cerebral artery segments of middle cerebral artery) after successful thrombectomy (modified Treatment In Cerebral Ischemia grades 2b-3). Microembolic signals (MES) were assessed by 30 minutes of transcranial Doppler monitoring within 72 hours of the last-seen-well time. Major outcomes included modified Rankin Scale at 90 days and infarct volume on head computed tomography at 24 hours. We also assessed early outcomes based on National Institutes of Health Stroke Scale variation and recurrence of stroke, transient ischemic attack, or systemic embolism within 90 days. Results- Among 111 patients, MES were detected in 43 (39%), with a median rate of 4 counts/h (interquartile range 2-12). The occurrence of MES was not associated with a significant difference in modified Rankin Scale (ordinal shift analysis, adjusted odds ratio, 1.06 [95% CI, 0.48-2.34] P=0.85) nor in functional independence (modified Rankin Scale, 0-2: adjusted odds ratio, 0.52 [95% CI, 0.19-1.39] P=0.19). Patients with and without MES had similar infarct volumes (adjusted beta, 11.2 [95% CI, -46.6 to +22.9] P=0.51) on 24-hour computed tomography. MES did predict new embolic events (adjusted Cox hazard ratio, 6.78 [95% CI, 1.63-27.8] P=0.01). Conclusions- MES detected by transcranial Doppler following endovascular treatment of anterior circulation occlusions do not predict clinical or radiological outcome. However, such emboli are an independent marker of recurrent embolic events within 90 days.

Revisiting human cerebral blood flow responses to augmented blood pressure oscillations.

KEY POINTS: Cerebral autoregulation is most effective in buffering against pressure fluctuations slower than 0.03 Hz (∼30 s). This suggests that frequency bands for characterizing cerebral autoregulation should be redefined Low cross-spectral coherence below 0.03 Hz highlights the limitations of transfer function approaches Haemodynamic changes induced by lower body pressure could not fully explain the differences in autoregulation estimated from spontaneous vs. augmented fluctuations, and thus, observations of spontaneous fluctuations should not be relied on whenever possible. ABSTRACT: There is currently little empirical basis for time scales that are considered to be most significant in cerebrovascular counter-regulation of changes in arterial pressure. Although it is well established that cerebral autoregulation behaves as a 'high-pass' filter, recommended frequency bands have been largely arbitrarily determined. To test effectiveness of cerebral autoregulation, we refined oscillatory lower body pressure (LBP) to augment resting pressure fluctuations below 0.1 Hz by a factor of two in 13 young male volunteers, and thoroughly characterized the time and frequency responses of cerebral autoregulation. We observed that despite a threefold increase in arterial pressure power <0.03 Hz with oscillatory LBP, there was no change in cerebral blood flow power, indicating near perfect counter-regulation. By contrast, in the range 0.03-0.10 Hz, both cerebral blood flow and arterial pressure power more than doubled. Our data demonstrate that cerebral autoregulation is most effective in buffering against pressure fluctuations slower than 0.03 Hz (∼30 s). This suggests that frequency bands of interest should be redefined and recording length should be increased considerably to account for this. Furthermore, low cross-spectral coherence below 0.03 Hz, even when pressure fluctuations were augmented, highlights the uncertainty in transfer function approaches and the need to either report precision or use non-linear approaches. Finally, haemodynamic changes induced by LBP could not fully explain the differences in autoregulation estimated from spontaneous vs. augmented fluctuations, and thus, observations of spontaneous fluctuations should not be relied on whenever possible.

Spot and Diffuse Signs: Quantitative Markers of Intracranial Hematoma Expansion at Dual-Energy CT.

Purpose To compare dual-energy CT with iodine quantification to single-energy CT for evaluation of the spot sign for intracranial hematoma expansion. Materials and Methods In this retrospective study, 42 patients (mean age, 66 years ± 15 [standard deviation]; 19 women) were referred for dual-energy CT assessment of intracranial hemorrhage from October 2014 to January 2017. A machine learning approach (naive Bayes classifier) was used to identify iodine markers of extravasation for risk of hematoma expansion. Specificity and sensitivity of these markers were then independently validated in 65 new patients from February 2017 to February 2018. Results Analysis of dual-energy CT images identified two features of iodine extravasation: total iodine concentration within the hematoma (Ih) and focal iodine concentration in the brightest spot in the hematoma (Ibs) as predictors of expansion. The I2 score derived from these features provided a measure of expansion probability. Optimal classification threshold was an I2 score of 20 (95% confidence interval [CI]: 18, 23), leading to correct identification of 39 of 46 (85%; 95% CI: 71%, 94%) of the hematomas on the training set (sensitivity of 79% [11 of 14; 95% CI: 57%, 100%] and specificity of 88% [28 of 32; 95% CI: 76%, 99%]), and 62 of 70 (89%; 95% CI: 79%, 95%) of the hematomas on the validation set (sensitivity of 71% [10 of 14; 95% CI: 48%, 95%] and specificity of 93% [52 of 56; 95% CI: 86%, 100%]). Sensitivity, specificity, and accuracy of conventional spot sign were, respectively, 57% (eight of 14), 90% (29 of 32), and 80% (37 of 46) on the training set and 57% (eight of 14), 83% (47 of 56), and 75% (53 of 70) on the validation set. Conclusion This study identified two quantitative markers of intracranial hemorrhage expansion at dual-energy CT of the brain. The I2 score derived from these markers highlights the utility of dual-energy CT measurements of iodine content for high sensitivity risk assessment. © RSNA, 2018 Online supplemental material is available for this article.

Traumatic Microbleeds in the Hippocampus and Corpus Callosum Predict Duration of Posttraumatic Amnesia.

OBJECTIVE: Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. SETTING: Academic, tertiary medical center. PARTICIPANTS: Adults with traumatic brain injury (TBI). DESIGN: We identified 65 TBI patients with acute GRE MRI. PTA duration was determined with the Galveston Orientation and Amnesia Test, Orientation Log, or chart review. TMBs were identified within memory regions (hippocampus, corpus callosum, fornix, thalamus, and temporal lobe) and control regions (internal capsule and global). Regression tree analysis was performed to identify radiologic predictors of PTA duration, controlling for clinical PTA predictors. MAIN MEASURES: TMB distribution, PTA duration. RESULTS: Sixteen patients (25%) had complicated mild, 4 (6%) had moderate, and 45 (69%) had severe TBI. Median PTA duration was 43 days (range, 0-240 days). In univariate analysis, PTA duration correlated with TMBs in the corpus callosum (R = 0.29, P = .02) and admission Glasgow Coma Scale (GCS) score (R = -0.34, P = .01). In multivariate regression analysis, admission GCS score was the only significant contributor to PTA duration. However, in regression tree analysis, hippocampal TMBs, callosal TMBs, age, and admission GCS score explained 26% of PTA duration variance and distinguished a subgroup with prolonged PTA. CONCLUSIONS: Hippocampal and callosal TMBs are potential radiologic predictors of PTA duration.

A pilot randomized controlled trial of 6-week combined exercise program on fasting insulin and fitness levels in individuals with spinal cord injury.

PURPOSE: The aim of this randomized controlled trial study was to investigate the effect of combined exercise program on the fasting insulin and fitness levels of people with spinal cord injury (SCI). METHODS: A total of 19 individuals with SCI participated in a combined exercise program consisting of aerobic and resistance exercises for 60 min per day, 3 days per week for 6 weeks. Peak oxygen consumption, body mass index, percent body fat, waist circumference, shoulder abduction and adduction, shoulder flexion and extension, elbow flexion and extension, fasting insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) levels were measured at baseline and after the intervention. RESULTS: The 6-week exercise program significantly decreased the average fasting insulin (baseline: 7.5 ± 4.7 µU/ml vs. post-intervention: 4.5 ± 2.2 µU/ml, p < 0.05) and HOMA-IR (baseline: 1.5 ± 1.0 vs. post-intervention: 0.9 ± 0.4, p < 0.05) in the exercise group, whereas there was no change in control group (between group difference, mean fasting insulin: - 3.2 µU/ml, p = 0.003; mean HOMA-IR: - 0.66, p = 0.001). In addition, muscle strength of the shoulder flexors, extensors, abductors, adductors, and elbow flexors was significantly improved in the exercise group compared to the controls. CONCLUSION: A combined exercise program is effective in decreasing fasting insulin and HOMA-IR levels while improving fitness in those with SCI. These slides can be retrieved under Electronic Supplementary Material.

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role for Hypoxia-Inducible Transcription Factor-1-Regulated Pathways.

BACKGROUND AND PURPOSE: Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether hypoxia-inducible transcription factor-1 activation may be temporally correlated with vascular changes. METHODS: We assessed cerebrovascular function (autoregulation, vasoreactivity, and neurovascular coupling) and serum concentrations of vascular endothelial growth factor and erythropoietin, as representative measures of hypoxia-inducible transcription factor-1 activation, during 6 hours of deferoxamine infusion in 24 young and 24 older healthy volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. Vascular endothelial growth factor and erythropoietin serum protein assays were conducted using the Meso Scale Discovery platform. RESULTS: Deferoxamine elicited a strong age- and time-dependent increase in the plasma concentrations of erythropoietin and vascular endothelial growth factor, which persisted ≤3 hours post infusion (age effect P=0.04; treatment×time P<0.01). Deferoxamine infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment×time P<0.01; age P<0.01) and cerebral autoregulation (gain: age×time×treatment P=0.04). CONCLUSIONS: Deferoxamine infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum vascular endothelial growth factor and erythropoietin concentrations is supportive of shared hypoxia-inducible transcription factor-1-regulated pathways. Therefore, pharmacological activation of hypoxia-inducible transcription factor-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT013655104.

Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review.

BACKGROUND: Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion. REVIEW METHOD: A narrative and systematic review of articles published in the English language, from December 1982 to October 2013. DATA SOURCES: Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included. RESULTS: Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US. CONCLUSIONS: These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion.

Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation.

BACKGROUND AND PURPOSE: Prior work aimed at improving our understanding of human cerebral autoregulation has explored individual physiological mechanisms of autoregulation in isolation, but none has attempted to consolidate the individual roles of these mechanisms into a comprehensive model of the overall cerebral pressure-flow relationship. METHODS: We retrospectively analyzed this relationship before and after pharmacological blockade of α-adrenergic-, muscarinic-, and calcium channel-mediated mechanisms in 43 healthy volunteers to determine the relative contributions of the sympathetic, cholinergic, and myogenic controllers to cerebral autoregulation. Projection pursuit regression was used to assess the effect of pharmacological blockade on the cerebral pressure-flow relationship. Subsequently, ANCOVA decomposition was used to determine the cumulative effect of these 3 mechanisms on cerebral autoregulation and whether they can fully explain it. RESULTS: Sympathetic, cholinergic, and myogenic mechanisms together accounted for 62% of the cerebral pressure-flow relationship (P<0.05), with significant and distinct contributions from each of the 3 effectors. ANCOVA decomposition demonstrated that myogenic effectors were the largest determinant of the cerebral pressure-flow relationship, but their effect was outside of the autoregulatory region where neurogenic control appeared prepotent. CONCLUSIONS: Our results suggest that myogenic effects occur outside the active region of autoregulation, whereas neurogenic influences are largely responsible for cerebral blood flow control within it. However, our model of cerebral autoregulation left 38% of the cerebral pressure-flow relationship unexplained, suggesting that there are other physiological mechanisms that contribute to cerebral autoregulation.