Brain-Blood Partition Coefficient and Cerebral Blood Flow in Canines Using Calibrated Short TR Recovery (CaSTRR) Correction Method.

The brain-blood partition coefficient (BBPC) is necessary for quantifying cerebral blood flow (CBF) when using tracer based techniques like arterial spin labeling (ASL). A recent improvement to traditional MRI measurements of BBPC, called calibrated short TR recovery (CaSTRR), has demonstrated a significant reduction in acquisition time for BBPC maps in mice. In this study CaSTRR is applied to a cohort of healthy canines (n = 17, age = 5.0 - 8.0 years) using a protocol suited for application in humans at 3T. The imaging protocol included CaSTRR for BBPC maps, pseudo-continuous ASL for CBF maps, and high resolution anatomical images. The standard CaSTRR method of normalizing BBPC to gadolinium-doped deuterium oxide phantoms was also compared to normalization using hematocrit (Hct) as a proxy value for blood water content. The results show that CaSTRR is able to produce high quality BBPC maps with a 4 min acquisition time. The BBPC maps demonstrate significantly higher BBPC in gray matter (0.83 ± 0.05 mL/g) than in white matter (0.78 ± 0.04 mL/g, p = 0.006). Maps of CBF acquired with pCASL demonstrate a negative correlation between gray matter perfusion and age (p = 0.003). Voxel-wise correction for BBPC is also shown to improve contrast to noise ratio between gray and white matter in CBF maps. A novel aspect of the study was to show that that BBPC measurements can be calculated based on the known Hct of the blood sample placed in scanner. We found a strong correlation (R 2 = 0.81 in gray matter, R 2 = 0.59 in white matter) established between BBPC maps normalized to the doped phantoms and BBPC maps normalized using Hct. This obviates the need for doped water phantoms which simplifies both the acquisition protocol and the post-processing methods. Together this suggests that CaSTRR represents a feasible, rapid method to account for BBPC variability when quantifying CBF. As canines have been used widely for aging and Alzheimer's disease studies, the CaSTRR method established in the animals may further improve CBF measurements and advance our understanding of cerebrovascular changes in aging and neurodegeneration

Improvements In computed tomography perfusion output using complex singular value decomposition and the maximum slope algorithm

OBJECTIVE: Determine if complex singular value decomposition (cSVD) used as preprocessing in the maximum slope algorithm reduces image noise of resultant physiologic parametric images. Noise will be decreased in the parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV) as compared to the same algorithm and data set with no cSVD applied. MATERIALS AND METHODS: A set of 10 patients (n=15) underwent a total combined 15 CT perfusion studies upon presenting with stroke symptoms. It was determined these patients suffered from occlusions resulting in a prolonged arrival time of blood to the brain. DICOM data files of these patients scans were selected based on this increased arrival delay. We compared the output of estimation calculations for cerebral blood flow (CBF), and cerebral blood volume (CBV), using preprocessing cSVD against the same scan data with no preprocessing cSVD. Image noise was assessed through the calculation of the standard deviation within specific regions of interest copied to specific areas of grey and white matter as well as CSF space. A decrease in the standard deviation values will indicate improvement in the noise level of the resultant images.. Results for the mean value within the regions of interest are expected to be similar between the groups calculated using cSVD and those calculated under the standard method. This will indicate the presence of minimal bias. RESULTS: Between groups of the standard processing method and the cSVD method standard deviation (SD) reductions were seen in both CBF and CBV values across all three ROIs. In grey matter measures of CBV, SD was reduced an average of 0.0034 mL/100g while measures of CBF saw SD reduced by an average of 0.073 mL/100g/min. In samples of white matter, standard deviations of CBV values were reduced on average by 0.0041mL/100g while CBF SD's were reduced by 0.073 mL/100g/min. CSF ROIs in CBV calculations saw SD reductions averaging 0.0047 mL/100g and reductions of 0.074 mL/100g/min in measures of CBF. Bias within CBV calculations was at most minimal as determined by no significant changes in mean calculated values. Calculations of CBF saw large downward bias in the mean values. CONCLUSIONS: The application of the cSVD method to preprocessing of CT perfusion imaging studies produces an effective method of noise reduction. In calculations of CBV, cSVD noise reduction results in overall improvement. In calculations of CBF, cSVD, while effective in noise reduction, caused mean values to be statistically lower than the standard method. It should be noted that there is currently no evaluation of which values can be considered more accurate physiologically. Simulations of the effect of noise on CBF showed a positive correlation suggesting that the CBF algorithm itself is sensitive to the level of noise

The effects of hemodynamic lag on functional connectivity and behavior after stroke

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance

Quality and validity of large animal experiments in stroke : a systematic review

An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models

ICA-based denoising for ASL perfusion imaging

Arterial Spin Labelling (ASL) imaging derives a perfusion image by tracing the accumulation of magnetically labeled blood water in the brain. As the image generated has an intrinsically low signal to noise ratio (SNR), multiple measurements are routinely acquired and averaged, at a penalty of increased scan duration and opportunity for motion artefact. However, this strategy alone might be ineffective in clinical settings where the time available for acquisition is limited and patient motion are increased. This study investigates the use of an Independent Component Analysis (ICA) approach for denoising ASL data, and its potential for automation.72 ASL datasets (pseudo-continuous ASL; 5 different post-labeling delays: 400, 800, 1200, 1600, 2000 m s; total volumes = 60) were collected from thirty consecutive acute stroke patients. The effects of ICA-based denoising (manual and automated) where compared to two different denoising approaches, aCompCor, a Principal Component-based method, and Enhancement of Automated Blood Flow Estimates (ENABLE), an algorithm based on the removal of corrupted volumes. Multiple metrics were used to assess the changes in the quality of the data following denoising, including changes in cerebral blood flow (CBF) and arterial transit time (ATT), SNR, and repeatability. Additionally, the relationship between SNR and number of repetitions acquired was estimated before and after denoising the data.The use of an ICA-based denoising approach resulted in significantly higher mean CBF and ATT values (p [less than] 0.001), lower CBF and ATT variance (p [less than] 0.001), increased SNR (p [less than] 0.001), and improved repeatability (p [less than] 0.05) when compared to the raw data. The performance of manual and automated ICA-based denoising was comparable. These results went beyond the effects of aCompCor or ENABLE. Following ICA-based denoising, the SNR was higher using only 50% of the ASL-dataset collected than when using the whole raw data.The results show that ICA can be used to separate signal from noise in ASL data, improving the quality of the data collected. In fact, this study suggests that the acquisition time could be reduced by 50% without penalty to data quality, something that merits further study. Independent component classification and regression can be carried out either manually, following simple criteria, or automatically

Whole-brain vasculature reconstruction at the single capillary level

The distinct organization of the brain’s vascular network ensures that it is adequately supplied with oxygen and nutrients. However, despite this fundamental role, a detailed reconstruction of the brain-wide vasculature at the capillary level remains elusive, due to insufficient image quality using the best available techniques. Here, we demonstrate a novel approach that improves vascular demarcation by combining CLARITY with a vascular staining approach that can fill the entire blood vessel lumen and imaging with light-sheet fluorescence microscopy. This method significantly improves image contrast, particularly in depth, thereby allowing reliable application of automatic segmentation algorithms, which play an increasingly important role in high-throughput imaging of the terabyte-sized datasets now routinely produced. Furthermore, our novel method is compatible with endogenous fluorescence, thus allowing simultaneous investigations of vasculature and genetically targeted neurons. We believe our new method will be valuable for future brain-wide investigations of the capillary network

The Impact of Inter-Hospital Transfer on Clinical Outcomes following Endovascular Treatment for Acute Ischemic Stroke

PURPOSE Hospitals designated as primary stroke centers offer noninvasive treatment for acute ischemic stroke, but only comprehensive stroke centers are equipped to provide endovascular treatment. When stroke patients needing endovascular treatment present to the emergency department at a primary stroke center, they then require inter-hospital transfer to a comprehensive center for definitive treatment. Recent studies have found significant treatment delays and poor clinical outcomes in patients requiring inter-hospital transfer1,2. The primary aim of this study is to determine if inter-hospital transfer impacts clinical outcomes after endovascular treatment for acute ischemic stroke. A secondary aim is to determine whether inter-hospital transfer coincides with any significant treatment delay. METHODS This study involves retrospective chart review for 107 patients undergoing endovascular treatment for acute ischemic stroke at one of three hospitals in Austin, Texas from October 2016 to September 2018. 26 patients required inter-hospital transfer, while 81 (the control group) presented directly to a hospital offering endovascular treatment. Two-tailed T- and U-tests were used for analysis of parametric and non-parametric variables pertaining to time intervals and baseline characteristics. Odds ratios were calculated to compare dichotomized outcomes between groups, with significance determined by chi-square. RESULTS Inter-hospital transfer significantly prolonged onset to groin (mean difference = 37.2 min, p=.02). The transfer group was more likely to experience intracranial hemorrhage (53.9% > 22.2%, p<.01). Clinical outcomes did not significantly differ between groups. CONCLUSIONS Although observed trends in these data suggest poor outcomes for transfer patients, small sample size limits the significance of these findings. However, the significant treatment delay seen in the transfer group warrants a discussion on city protocol changes regarding patient transport via emergency services. Protocol changes favoring direct delivery of patients to comprehensive stroke centers may reduce treatment delay and yield improved clinical outcomes.Dell Medical Schoo

Dissociation of Cerebral Blood Flow and Femoral Artery Blood Pressure Pulsatility After Cardiac Arrest and Resuscitation in a Rodent Model: Implications for Neurological Recovery.

Background Impaired neurological function affects 85% to 90% of cardiac arrest (CA) survivors. Pulsatile blood flow may play an important role in neurological recovery after CA. Cerebral blood flow (CBF) pulsatility immediately, during, and after CA and resuscitation has not been investigated. We characterized the effects of asphyxial CA on short-term (&lt;2&nbsp;hours after CA) CBF and femoral arterial blood pressure (ABP) pulsatility and studied their relationship to cerebrovascular resistance (CVR) and short-term neuroelectrical recovery. Methods and Results Male rats underwent asphyxial CA followed by cardiopulmonary resuscitation. A multimodal platform combining laser speckle imaging, ABP, and electroencephalography to monitor CBF, peripheral blood pressure, and brain electrophysiology, respectively, was used. CBF and ABP pulsatility and CVR were assessed during baseline, CA, and multiple time points after resuscitation. Neuroelectrical recovery, a surrogate for neurological outcome, was assessed using quantitative electroencephalography 90&nbsp;minutes after resuscitation. We found that CBF pulsatility differs significantly from baseline at all experimental time points with sustained deficits during the 2&nbsp;hours of postresuscitation monitoring, whereas ABP pulsatility was relatively unaffected. Alterations in CBF pulsatility were inversely correlated with changes in CVR, but ABP pulsatility had no association to CVR. Interestingly, despite small changes in ABP pulsatility, higher ABP pulsatility was associated with worse neuroelectrical recovery, whereas CBF pulsatility had no association. Conclusions Our results reveal, for the first time, that CBF pulsatility and CVR are significantly altered in the short-term postresuscitation period after CA. Nevertheless, higher ABP pulsatility appears to be inversely associated with neuroelectrical recovery, possibly caused by impaired cerebral autoregulation and/or more severe global cerebral ischemia