Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Confirmatory Study of Time-Dependent Computed Tomographic Perfusion Thresholds for Use in Acute Ischemic Stroke.

Background and Purpose- Computed tomographic perfusion (CTP) thresholds associated with follow-up brain infarction may differ by time from symptom onset to imaging and reperfusion. We confirm CTP thresholds over time to imaging and reperfusion in patients with acute ischemic stroke from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) data. Methods- Patients with occlusion on CT angiography were acutely imaged with CTP. Noncontrast CT and magnetic resonance-diffusion weighted imaging at 24 to 48 hours defined follow-up infarction. Reperfusion was assessed on conventional angiogram. Tmax, cerebral blood flow (CBF), and cerebral blood volume maps were derived from delay-insensitive CTP postprocessing. These parameters were analyzed using receiver operator characteristics to derive optimal thresholds based on time from stroke onset-to-CTP or to reperfusion. ANOVA and linear regression were used to test whether the derived CTP thresholds were different by time. Results- One hundred thirty-seven patients were included. Tmax thresholds of >15.7 s and >15.8 s and absolute CBF thresholds of <8.9 and <7.5 mL·min-1·100 g-1 for gray matter and white matter respectively were associated with infarct if reperfusion was achieved <90 minutes from CTP with stroke onset-to-CTP <180 minutes. The discriminative ability of cerebral blood volume was modest. There were no statistically significant relationships between stroke onset-to-CTP time and Tmax, CBF, and cerebral blood volume thresholds (all P>0.05). A statistically significant relationship was observed between CTP-to-reperfusion time and the optimal thresholds for Tmax (P<0.001) and CBF (P<0.001). Similar but more modest relationship was noted for onset-to-reperfusion time and optimal thresholds for CBF (P≤0.01). Conclusions- CTP thresholds based on stroke onset and imaging time and taking into account time needed for reperfusion may improve infarct prediction in patients with acute ischemic stroke.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. METHODS: Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. RESULTS: One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. CONCLUSIONS: Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator.

BACKGROUND AND PURPOSE: Thrombolysis depends on the ability of blood and thrombolytic agents to permeate thrombus. We devised a novel technique to quantify blood permeating through thrombi and determine whether this parameter predicts early recanalization with intravenous tissue-type plasminogen activator. METHODS: Intravenous tissue-type plasminogen activator-treated patients with stroke and complete occlusion on computed tomographic angiography were analyzed using perfusion computed tomography and a delay insensitive algorithm. We generated maps that measure delay in arrival time of contrast within the intracranial arterial tree (T0 maps). A positive sloped regression line of T0 values measured along artery silhouette distal to thrombus was defined as marker of permeable thrombus (occult anterograde flow). Median T0 values at proximal and distal thrombus interface were measured. Early recanalization was assessed on first angiography of subsequent intra-arterial procedure or on a 4-hour computed tomographic angiography. RESULTS: Of 66 patients, occult anterograde flow was detected in 17 (25.8%). Early recanalization was more in patients with occult anterograde flow versus not (66.7 versus 29.7%; P=0.031). Median T0 value (in s) at distal thrombus interface (1.5 versus 3.8; P=0.006) and difference in median T0 value between proximal and distal thrombus interface (1.3 versus 3.7; P=0.014) were less in early recanalizers versus in nonrecanalizers. In multivariable analysis, patients with occult anterograde flow and T0 value difference between proximal and distal thrombus interface ≤2 s recanalized most (71.4%; odds ratio, 12.15; 95% confidence interval, 2.05-71.91), whereas patients with retrograde flow and T0 value difference >2 s recanalized least (25.9%; odds ratio, 1). CONCLUSIONS: Occult anterograde flow through thrombus can be assessed by perfusion computed tomography T0 maps and predicts early recanalization with intravenous tissue-type plasminogen activator robustly.

The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial: ICH ADAPT.

The majority of intracerebral haemorrhage patients present with markedly elevated blood pressure immediately after symptom onset. Management of blood pressure in the first 24 h is extremely controversial and lends itself to two competing rationales. There is some evidence that early treatment may improve outcome, potentially by reducing the rate of haematoma expansion. It is also possible that this will reduce cerebral blood flow and therefore exacerbate the cerebral injury, particularly in the region surrounding the haematoma. Only a trial that includes both randomisation of patients to two different blood pressure management strategies and actual measurement of cerebral blood flow can effectively address this pressing debate. This is the only unequivocal way to demonstrate the haemodynamic effects of rapid blood pressure reduction. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial is designed to test the hypothesis that blood pressure reduction does not result in significant or harmful changes in cerebral blood flow in acute intracerebral haemorrhage. Two hours after randomisation to a systolic blood pressure target of <150 or <180 mmHg, cerebral blood flow is measured using computed tomography perfusion, which is the primary end-point of the trial. A study of this type is critical to establishing the safety of early blood pressure treatment and is necessary for planning larger efficacy trials in a rational manner. This trial is registered with clinicaltrials.gov (NCT00963976).

Predicting postoperative FEV1 using spiral computed tomography.

RATIONALE AND OBJECTIVES: Lung resection for primary bronchogenic carcinoma in the setting of chronic obstructive pulmonary disease often requires a detailed assessment of lung function to avoid perioperative complications and long-term disability. The aim of this study was to test the hypothesis that a novel technique of spiral computed tomographic (CT) subtraction imaging provides accuracy equal to the current standard of radioisotope perfusion scintigraphy in predicting postoperative lung function. METHODS AND MATERIALS: Preoperative lung function, radioisotope perfusion scintigraphy, spiral CT subtraction imaging, and assessment of postoperative lung function were performed in 25 patients with surgically resectable primary bronchogenic carcinoma. Comparisons of predicted postoperative lung function between the two modalities and to true postoperative lung function were performed using Pearson's correlation and linear regression analysis. RESULTS: Among the 25 patients enrolled in the study, there was a high degree of agreement between the predicted value of postoperative forced expiratory lung volume in 1 second (FEV(1)) generated on novel contrast CT subtraction imaging and that on radioisotope perfusion scintigraphy (r = 0.96, P < .001). Furthermore, there was a strong correlation between the predicted and actual postoperative FEV(1) values for both imaging modalities (r = 0.87, P < .001, and r = 0.88, P < .001, respectively), among the 14 patients completing the study protocol. CONCLUSION: A novel technique of CT subtraction imaging is equally accurate at predicting postoperative lung function as radioisotope perfusion scintigraphy, which may obviate the need for additional nuclear imaging in the context of the preoperative assessment of resectable lung cancer in high-risk patients.

The effects of botulinum toxin type A on muscle blood perfusion and metabolism.

BACKGROUND: Botulinum toxin type A is approved by the U.S. Food and Drug Administration for the treatment of facial rhytides. However, the complete spectrum of action of botulinum toxin A has not yet been completely defined. Little is known about the metabolism of muscle after botulinum toxin A injection. This information may give insight into the additional effects botulinum toxin A may have on muscle. The authors assessed the influence of botulinum toxin A on the metabolism of muscle using dynamic investigative techniques. METHODS: Twenty New Zealand White rabbits were divided into control, paralysis, and sham groups. Masseter muscle paralysis was achieved with botulinum toxin A. Dynamic computed tomographic and positron emission tomographic scans were obtained. Masseter muscle blood flow, blood volume, permeability surface, and mean transit time and glucose uptake were measured. RESULTS: Eighteen animals completed the study. Masseter blood perfusion showed consistent results across all parameters. Blood flow, blood volume, and permeability surface were significantly increased at weeks 4 and 8 on the paralyzed side. Mean transit time at week 4 was decreased on the paralyzed side. Positron emission tomographic scans showed that injected muscles in the botulinum toxin A group tended to have increased glucose uptake compared with untreated muscles. CONCLUSIONS: Botulinum toxin A injection increases muscle blood perfusion parameters and glucose uptake for a transient period. This increase is similar in duration to the known interval of botulinum toxin A-induced paralysis. These changes have been identified in a dynamic fashion and may represent changes in calcitonin gene-related peptide release.

The effects of masseter muscle paralysis on facial bone growth.

BACKGROUND: Understanding the effects of muscle function on facial bone growth may help us treat children with facial anomalies. Facial bone growth is known to be a result of both genetic and epigenetic influences. One of the main epigenetic factors controlling growth is thought to be muscle action. The purpose of this study was to establish a model of single facial muscle paralysis and to identify the effects masseter muscle paralysis has on mandible and zygoma growth. METHODS: Twenty New Zealand white rabbits were divided into control, paralysis, and sham groups. Masseter muscle paralysis was achieved with botulinum toxin A (BTX). Computed tomographic and single-photon emission computed tomography (SPECT) scans and cephalometric measurements were performed. Masseter weights and mandible and zygoma volumes, shapes, and metabolism were measured. RESULTS: Eighteen animals completed the study. Significant decreases in zygoma and mandible volumes with minimal changes in shape were seen on the paralyzed sides. SPECT showed a decrease in bone production in both zygomas and mandibles on the paralyzed sides. CONCLUSIONS: An animal model has been created in which the effects of single muscle paralysis on bone growth can be studied. Masseter muscle function may be responsible in maintaining mandible and zygoma volume by controlling bone production. Masseter function alone has less influence on mandible and zygoma shape.

Functional CT for quantifying tumor perfusion in antiangiogenic therapy in a rat model.

PURPOSE: To determine the histologic basis of perfusion parameters measured at functional computed tomography (CT) and to examine the relationship between changes in perfusion and changes in histologic parameters after antiangiogenic therapy in a rat model. MATERIALS AND METHODS: This study had institutional animal care and use committee approval. Among 20 Fischer rats with implanted FN13762 tumors in the liver, 10 were treated with SU5416, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, and 10 were treated with the diluent only as control rats. Six rats chosen at random from each group underwent functional CT for the measurement of tumor blood flow, blood volume, mean transit time, and permeability-surface area product. Tumor tissue slides corresponding to functional CT sections were examined to measure tumor microvascular density, number of luminal vessels, vascular perimeter, and vascular area. Two-tailed Student t testing was used to determine differences in growth, numbers of metastases to major organs, vascularity, and perfusion between SU5416-treated and control tumors. Pearson correlation coefficients were used to investigate relationships between vascular parameters. RESULTS: Mean tumor volume and number of metastases, respectively, were lower in SU5416-treated rats than in control rats (1580 mm3 +/- 830 [standard deviation] vs 2330 mm3 +/- 960 and 22.4 +/- 11.0 vs 35.2 +/- 17.3); however, these differences were not significant (P = .084 and P = .079). Mean tumor microvascular density was significantly lower in SU5416-treated rats than in control rats (6.4 vessels per field +/- 4.6 vs 17.2 vessels per field +/- 7.5, P < .001); however, vessel perimeter and vessel area, respectively, were significantly larger in treated rats than in control rats (470 microm per field +/- 320 vs 360 microm per field +/- 270, P = .02; and 4010 microm2 per field +/- 2990 vs 2230 microm2 per field +/- 1750, P = .001). Significant correlations were observed between microvascular density and vessel perimeter and area (r = 0.59 and r = 0.25, respectively; P < .01 for both) in SU5416-treated tumors but not control tumors. Blood flow, blood volume, and permeability-surface area product at functional CT were significantly higher in SU5416-treated tumors than in control tumors (P < .001 for all). CONCLUSION: These results validate the idea that functional CT can help quantify the perfusion function of mature vessels but not changes in microvessel density in antiangiogenic therapy.

Assessment of the tumor microenvironment in cervix cancer using dynamic contrast enhanced CT, interstitial fluid pressure and oxygen measurements.

PURPOSE: Interstitial fluid pressure (IFP) and oxygen (pO(2)) measurements are prognostic factors in cervical cancer. The purpose of this study was to determine the relationship between IFP and oxygenation and parameters derived from dynamic contrast-enhanced computed tomography (DCE-CT). METHODS AND MATERIALS: Dynamic contrast-enhanced computed tomography was performed in 32 patients with cervical cancer before radiation therapy. Images were acquired during intravenous contrast injection at 1 per s for 120 s and 1 per 15 s for 60 s. DCE-CT was analyzed using CT Perfusion 3 software (GE Medical Systems) to derive tumor blood flow (BF), permeability surface area product, blood volume, and mean transit time. Further analysis was performed to obtain relative peak enhancement, residual enhancement at 3 min after contrast injection (RE), time to peak and initial slope. Nodal status and tumor size were assessed with MRI. From in vivo IFP (n = 31) and pO(2) (n = 31) tumor measurements median pO(2) (mO(2)), percentage measurements less than 5 mm Hg (HP5) and mean IFP values were calculated. RESULTS: There was a positive correlation between BF and mO(2) (r = 0.47, p = 0.007) and between RE and HP5 (r = 0.39, p = 0.03). There was no correlation between IFP and DCE-CT parameters. CONCLUSION: There is a moderately positive, correlation between tumor oxygenation and BF as well as RE and HP5. Further study is required to determine if DCE-CT parameters are useful predictors of tumor behavior in cervical cancer.

The effect of varying user-selected input parameters on quantitative values in CT perfusion maps.

RATIONALE AND OBJECTIVES: Deconvolution-based software can be used to calculate quantitative maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) from first-pass computed tomography perfusion (CTP) datasets. The application of this software requires the user to select multiple input variables. The purpose of this study was to investigate the degree to which both major and minor variations of these user-defined inputs would affect the final quantitative values of CBF, CBV, and MTT. MATERIALS AND METHODS: A neuroradiologist constructed CBF, CBV, and MTT maps using standard methodology with commercially available software (GE Functool Version 1.9s) from CTP datasets of three acute stroke patients. Each map was reconstructed multiple times by systematically and independently varying the following parameters: postenhancement and preenhancement cutoff values, arterial and venous region-of-interest (ROI) placement, and arterial and venous ROI size. The resulting quantitative CTP values were compared using identical ROIs placed at the infarct core. RESULTS: Major variations of either arterial ROI placement or arterial and venous ROI size had no significant effect on the mean CBF, CBV, and MTT values at the infarct core (p > .05). Even minor variations, however, in the choice of venous ROI placement or in pre- and postenhancement cutoff values significantly altered the quantitative values for each of the CTP maps, by as much as threefold. CONCLUSION: Even minor variations of user-defined inputs can significantly influence the quantitative, deconvolution-based CTP map values of acute stroke patients. Although quantitation was robust to the choice of arterial ROI placement and arterial or venous ROI size, it was strongly dependent on the choice of venous ROI location and pre- and postenhancement cut-off values. Awareness of these results by clinicians may be important in the creation of quantitatively accurate CTP maps.