Cihat Eldeniz

Early Changes of Tissue Perfusion After Tissue Plasminogen Activator in Hyperacute Ischemic Stroke

Background and Purpose— It is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome. Methods— Three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.5 (tp1), at 6 hours (tp2), and at 1 month (tp3) after stroke onset. “Hypoperfusion” was defined if mean transit time prolongation was more than a threshold (4 thresholds: 3, 4, 5, and 6 seconds). Four regions of interest were classified: (1) “reperfusion”—hypoperfused at tp1, normal at tp2; (2) “nonreperfusion”—hypoperfused at tp1 and tp2; (3) “normal perfusion”—normal at tp1 and tp2; and (4) “new hypoperfusion”—normal at tp1 and hypoperfused at tp2. Risk of infarction was calculated within each region of interest. Associations between tissue perfusion changes and clinical variables were evaluated using stepwise multiple linear regressions. Moreover, the association between National Institutes of Health Stroke Scale changes and perfusion alterations was assessed using linear mixed effect models. Results— Regardless of the mean transit time threshold chosen, the risk of infarction in nonreperfused regions (40% to 68%, thresholds 3 to 6 seconds) was higher than reperfused regions (9% to 30%, P<0.05), and it was higher in new hypoperfusion regions (9% to 33%) than normal perfusion regions (3% to 4%, P<0.05). Volume of new hypoperfusion was significantly associated with onset-to-treatment time and initial hypoperfused volume. Overall relative reperfusion was significantly associated with National Institutes of Health Stroke Scale improvement. Conclusion— Early tissue perfusion changes influenced final tissue fate. The development of new hypoperfusion may result from delay in tissue plasminogen activator and a large initial lesion.

Spatiotemporal Uptake Characteristics of [18]F-2-Fluoro-2-Deoxy-d-Glucose in a Rat Middle Cerebral Artery Occlusion Model

Background and Purpose— Alterations of cerebral glucose metabolism are well anticipated during cerebral ischemia. However, detailed spatiotemporal characteristics of disturbed cerebral glucose metabolism during acute ischemia remain largely elusive. This study aims to delineate spatiotemporal distributions of [18]F-2-fluoro-2-deoxy-D-glucose (FDG) uptake using positron emission tomography imaging, particularly at the peri-ischemic zone, and its correlation with tissue outcome. Methods— The intraluminal suture middle cerebral artery occlusion model was used to induce focal cerebral ischemia in rats (n=48). All animals underwent sequential MRI and FDG positron emission tomography imaging at different times (30–150 minutes) after middle cerebral artery occlusion. MR and positron emission tomography images were coregistered. FDG uptake in the peri-ischemic zone was assessed in relation to middle cerebral artery occlusion duration, cerebral blood flow, apparent diffusion coefficient, and 24-hour T2 lesions. Results— Elevated FDG uptake was consistently observed at the peri-ischemic zone surrounding the presumed ischemic core with low FDG uptake. Both the spatial volume and the uptake level of the hyper-uptake region were inversely correlated with the duration of middle cerebral artery occlusion. The hyper-uptake regions exhibited a mild reduction of cerebral blood flow (28.2±3.2%) and apparent diffusion coefficient (9.1±1.4%) when compared with that in the contralateral hemisphere. Colocalization analysis revealed that, with reperfusion, an average of 12.1±1.7% of the hyper-uptake volume was recruited into final infarction. Conclusions— Elevated FDG uptake at the peri-ischemic zone is consistently observed during acute cerebral ischemia. The region with elevated FDG uptake likely reflects viable tissues that can be salvaged with reperfusion. Therefore, acute FDG positron emission tomography imaging might hold promise in the management of patients with acute stroke.

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease

Objective To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD. Methods Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps. Results Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort. Conclusions Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia

Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.

Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue

Background and Purpose— We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome. Methods— Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT–[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp3 h), 6 (MTTp6 h), and 24 hours (MTTp24 h). Perfusion changes between 3 and 6 hours (&Dgr;MTTp3_6) and 6 and 24 hours (&Dgr;MTTp6_24) were calculated. A 2-step analysis was performed to evaluate the impact of &Dgr;MTTp3_6 and &Dgr;MTTp6_24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp3 h, &Dgr;MTTp3_6, and &Dgr;MTT6_24 as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether &Dgr;MTTp3_6 and &Dgr;MTT6_24 had significant impact on tissue fate for varying severities of baseline perfusion. Results— Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. &Dgr;MTT3_6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0–15 s). &Dgr;MTT6_24 also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0–10 s). Conclusions— Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows.

TOWERS: T-One with Enhanced Robustness and Speed.

A new T1 mapping method is proposed that is accurate, rapid, and robust to motion. Considering these features, the method is dubbed “T‐One with Enhanced Robustness and Speed (TOWERS).”

Comparison of cerebral blood volume and plasma volume in untreated intracranial tumors

Purpose Plasma volume and blood volume are imaging-derived parameters that are often used to evaluation intracranial tumors. Physiologically, these parameters are directly related, but their two different methods of measurements, T1-dynamic contrast enhanced (DCE)- and T2-dynamic susceptibility contrast (DSC)-MR utilize different model assumptions and approaches. This poses the question of whether the interchangeable use of T1-DCE-MRI derived fractionated plasma volume (vp) and relative cerebral blood volume (rCBV) assessed using DSC-MRI, particularly in glioblastoma, is reliable, and if this relationship can be generalized to other types of brain tumors. Our goal was to examine the hypothetical correlation between these parameters in three most common intracranial tumor types. Methods Twenty-four newly diagnosed, treatment naïve brain tumor patients, who had undergone DCE- and DSC-MRI, were classified in three histologically proven groups: glioblastoma (n = 7), meningioma (n = 9), and intraparenchymal metastases (n = 8). The rCBV was obtained from DSC after normalization with the normal-appearing anatomically symmetrical contralateral white matter. Correlations between these parameters were evaluated using Pearson (r), Spearmans (ρ) and Kendall’s tau-b (τB) rank correlation coefficient. Results The Pearson, Spearman and Kendall’s correlation between vp with rCBV were r = 0.193, ρ = 0.253 and τB = 0.33 (p-Pearson = 0.326, p-Spearman = 0.814 and p-Kendall = 0.823) in glioblastoma, r = -0.007, ρ = 0.051 and τB = 0.135 (p-Pearson = 0.970, p-Spearman = 0.765 and p-Kendall = 0.358) in meningiomas, and r = 0.289, ρ = 0.228 and τB = 0.239 (p-Pearson = 0.109, p-Spearman = 0.210 and p-Kendall = 0.095) in metastasis. Conclusion Results indicate that no correlation exists between vp with rCBV in glioblastomas, meningiomas and intraparenchymal metastatic lesions. Consequently, these parameters, as calculated in this study, should not be used interchangeably in either research or clinical practice.

CAPTURE: Consistently Acquired Projections for Tuned and Robust Estimation: A Self-Navigated Respiratory Motion Correction Approach

Objectives In this study, we present a fully automated and robust self-navigated approach to obtain 4-dimensional (4-D) motion-resolved images during free breathing. Materials and Methods The proposed method, Consistently Acquired Projections for Tuned and Robust Estimation (CAPTURE), is a variant of the stack-of-stars gradient-echo sequence. A 1-D navigator was consistently acquired at a fixed azimuthal angle for all stacks of spokes to reduce nonphysiological signal contamination due to system imperfections. The resulting projections were then “tuned” using complex phase rotation to adapt to scan-to-scan variations, followed by the detection of the respiratory curve. Four-dimensional motion-corrected and uncorrected images were then reconstructed via respiratory and temporal binning, respectively. This Health Insurance Portability and Accountability Act–compliant study was performed with Institutional Review Board approval. A phantom experiment was performed using a custom-made deformable motion phantom with an adjustable frequency and amplitude. For in vivo experiments, 10 healthy participants and 12 liver tumor patients provided informed consent and were imaged with the CAPTURE sequence. Two radiologists, blinded to which images were motion-corrected and which were not, independently reviewed the images and scored the image quality using a 5-point Likert scale. Results In the respiratory motion phantom experiment, CAPTURE reversed the effects of motion blurring and restored edge sharpness from 36% to 78% of that observed in the images from the static scan. Despite large intra- and intersubject variability in respiration patterns, CAPTURE successfully detected the respiratory motion signal in all participants and significantly improved the image quality according to the subjective radiological assessments of 2 raters (P < 0.05 for both raters) with a 1 to 2-point improvement in the median Likert scores across the whole set of participants. Small lesions (<1 cm in size) which might otherwise be missed on uncorrected images because of motion blurring were more clearly depicted on the CAPTURE images. Conclusions CAPTURE provides a robust and fully automated solution for obtaining 4-D motion-resolved images in a free-breathing setting. With its unique tuning feature, CAPTURE can adapt to large intersubject and interscan variations. CAPTURE also enables better lesion delineation because of improved image sharpness, thereby increasing the visibility of small lesions.

Estimating posterior image variance with sparsity-based object priors for MRI

Point estimates, such as the maximum a posteriori (MAP) estimate, are commonly computed in image re- construction tasks. However, such point estimates provide no information about the range of highly probable solutions, namely the uncertainty in the computed estimate. Bayesian inference methods that seek to compute the posterior probability distribution function (PDF) of the object can provide exactly this information, but are generally computationally intractable. Markov Chain Monte Carlo (MCMC) methods, which avoid explicit posterior computation by directly sampling from the PDF, require considerable expertise to run in a proper way. This work investigates a computationally efficient variational Bayesian inference approach for computing the posterior image variance with application to MRI. The methodology employs a sparse object prior model that is consistent with the model assumed in most sparse reconstruction methods. The posterior variance map generated by the proposed method provides valuable information that reveals how data-acquisition parameters and the specification of the object prior affect the reliability of a reconstructed MAP image. The proposed method is demonstrated by use of computer-simulated MRI data.