Variability assessment of manual segmentations of ischemic lesion volume on 24-h non-contrast CT

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

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Neuroprotective mechanisms of erythropoietin in a rat stroke model

Translational Neuroscience ◽

10.1515/tnsci-2020-0008 ◽

2020 ◽

Vol 11 (1) ◽

pp. 48-59

Author(s):

Martin Juenemann ◽

Tobias Braun ◽

Nadine Schleicher ◽

Mesut Yeniguen ◽

Patrick Schramm ◽

...

Keyword(s):

Blood Flow ◽

Infarct Size ◽

Cerebral Edema ◽

Infarct Volume ◽

Artery Occlusion ◽

Lesion Volume ◽

Ischemic Lesion ◽

Human Erythropoietin ◽

Male Wistar Rats ◽

Cerebral Artery Occlusion

AbstractObjectiveThis study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO).MethodsOne hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet–dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography.ResultsIn the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment.ConclusionsSingle-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

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Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.116.015156 ◽

2017 ◽

Vol 48 (5) ◽

pp. 1233-1240 ◽

Cited By ~ 20

Author(s):

Amber Bucker ◽

Anna M. Boers ◽

Joseph C.J. Bot ◽

Olvert A. Berkhemer ◽

Hester F. Lingsma ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Lesion Volume ◽

Ischemic Lesion

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Improving acute stroke assessment in non-enhanced CT: Automated tool for early ischemic lesion volume detection

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.119611 ◽

2021 ◽

Vol 429 ◽

pp. 119611

Author(s):

Giovanni Furlanis ◽

Mara Bernardi ◽

Alex Rodriguez ◽

Paola Caruso ◽

Marcello Naccarato ◽

...

Keyword(s):

Acute Stroke ◽

Lesion Volume ◽

Ischemic Lesion ◽

Enhanced Ct ◽

Automated Tool ◽

Stroke Assessment

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Clinical and Radiological Correlates of Reduced CBF Measured Using MRI

Stroke ◽

10.1161/str.32.suppl_1.317-a ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 317-318

Author(s):

Vincent N Thijs ◽

Tobias Neumann-Haefelin ◽

Michael E Moseley ◽

Michael P Marks ◽

Gregory W Albers

Keyword(s):

Symptom Onset ◽

Cerebral Blood Volume ◽

Arterial Input Function ◽

Mean Transit Time ◽

Input Function ◽

Lesion Volume ◽

Time Curve ◽

Measured Concentration ◽

Ischemic Lesion ◽

Adc Values

11 Background and purpose Methods for determining CBF using IV bolus tracking MRI have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional cerebral blood flow (rCBF). We studied the clinical and radiological features of patients with severe reductions of rCBF on MRI and analysed the relationship between reduced rCBF and ADC. Methods We studied patients with non-lacunar acute ischemic stroke in whom PWI and DWI MRI were performed within 7 hours after symptom onset. A PWI>DWI mismatch of >20% was required. Maps of rCBF, cerebral blood volume (rCBV) and mean transit time (rMTT) were generated after deconvoluting the measured concentration-time curve with the arterial input function using singular value decomposition. The ischemic lesion was outlined on the MTT map and the region of interest (ROI) transferred to the rCBF and rCBV map. ADC-maps were calculated. ADC lesions were defined as regions with ADC values ≤ 550 μm m2/sec. We compared the characteristics of patients with ischemic lesions that had a relative CBF of <50% to the contralateral hemisphere to patients with lesions that had relative CBF of >50%. Characteristics analysed included age, time to MRI, baseline NIHSS, mean ADC, DWI lesion volume, PWI lesion volume and absolute mismatch volume. Results Fifteen patients with an initial PWI>DWI mismatch of >20% were included. Ten had lesions with rCBF of >50% (median 60%) and five patients had rCBF of <50% (median 27.7%). Patients with rCBF <50% had lower ADC values (median 431 μmm2/sec versus 506 μ mm2/sec, p=0.028), larger DWI volumes (median 75.6 cm 3 versus 8.6 cm 3 , p=0.001) and larger PWI lesions as defined by the MTT volume (median 193 cm 3 versus 69 cm 3 , p=0.028) and more severe baseline NIHSS scores (median 18 versus 9, p=0.019). The rMTT and rCBV of the lesions were similar in both groups, as were the age, the absolute mismatch volume and the time from symptom onset to MRI. Conclusion These data indicate that ischemic lesions with severe CBF reductions, measured with new MRI techniques, are associated with a lower mean ADC, larger DWI and PWI lesion volumes and a higher NIHSS score.

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An exploratory investigation of brain collateral circulation plasticity after cerebral ischemia in two experimental C57BL/6 mouse models

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19827251 ◽

2019 ◽

Vol 40 (2) ◽

pp. 276-287 ◽

Cited By ~ 6

Author(s):

Marco Foddis ◽

Katarzyna Winek ◽

Kajetan Bentele ◽

Susanne Mueller ◽

Sonja Blumenau ◽

...

Keyword(s):

Carotid Artery ◽

Mouse Models ◽

Collateral Circulation ◽

Artery Occlusion ◽

External Carotid Artery ◽

External Carotid ◽

Lesion Volume ◽

Compensatory Mechanism ◽

Ischemic Lesion ◽

Acute Brain Ischemia

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60-min transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO, whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size.

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Prediction of Malignant Middle Cerebral Artery Infarction Using Computed Tomography-Based Intracranial Volume Reserve Measurements

Stroke ◽

10.1161/strokeaha.111.619734 ◽

2011 ◽

Vol 42 (12) ◽

pp. 3403-3409 ◽

Cited By ~ 66

Author(s):

Jens Minnerup ◽

Heike Wersching ◽

E. Bernd Ringelstein ◽

Walter Heindel ◽

Thomas Niederstadt ◽

...

Keyword(s):

Middle Cerebral Artery ◽

Cerebral Artery ◽

Predictive Value ◽

Perfusion Ct ◽

Lesion Volume ◽

Intracranial Volume ◽

Ischemic Lesion ◽

Predictive Values ◽

Malignant Infarction ◽

Malignant Mca Infarction

Background and Purpose— Early decompressive surgery in patients with malignant middle cerebral artery (MCA) infarction improves outcome. Elevation of intracranial pressure depends on both the space occupying brain edema and the intracranial volume reserve (cerebrospinal fluid [CSF]). However, CSF volume was not investigated as a predictor of malignant infarction so far. We hypothesize that assessment of CSF volume in addition to admission infarct size improves early prediction of malignant MCA infarction. Methods— Stroke patients with carotid-T or MCA main stem occlusion and ischemic lesion (reduced cerebral blood volume [CBV]) on perfusion CT were considered for the analysis. The end point malignant MCA infarction was defined by clinical signs of herniation. Volumes of CSF and CBV lesion were determined on admission. Receiver-operator characteristics analysis was used to calculate predictive values for radiological and clinical measurements. Results— Of 52 patients included, 26 (50%) developed malignant MCA infarction. Age, a decreased level of consciousness on admission, CBV lesion volume, CSF volume, and the ratio of CBV lesion volume to CSF volume were significantly different between malignant and nonmalignant groups. The best predictor of a malignant course was the ratio of CBV lesion volume to CSF volume with a cut-off value of 0.92 (96.2% sensitivity, 96.2% specificity, 96.2% positive predictive value, and 96.2% negative predictive value). Conclusions— Based on admission native CT and perfusion CT measurements, the ratio of ischemic lesion volume to CSF volume predicts the development of malignant MCA infarction with higher accuracy than other known predictors, including ischemic lesion volume or clinical characteristics.

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Angiopoietin-2 is Vasoprotective in the Acute Phase of Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.178 ◽

2012 ◽

Vol 33 (3) ◽

pp. 389-395 ◽

Cited By ~ 7

Author(s):

Léna Marteau ◽

Samuel Valable ◽

Didier Divoux ◽

Simon A Roussel ◽

Omar Touzani ◽

...

Keyword(s):

Cerebral Ischemia ◽

Acute Phase ◽

Focal Cerebral Ischemia ◽

Neurovascular Unit ◽

Protective Role ◽

Lesion Volume ◽

Ischemic Lesion ◽

Vessel Growth ◽

Angiopoietin 2

Most forms of cerebral ischemia are characterized by damage to the entire neurovascular unit, which leads to an increase in the permeability of the blood–brain barrier (BBB). In response to permanent focal cerebral ischemia in mice, we detected an early concomitant increase in the expression of the vascular endothelial growth factor (VEGF), a key inducer of vascular leakage and pathological blood vessel growth, and of angiopoietin-2 (Ang2), which is closely associated with VEGF in vascular remodeling. Thus, the aim of this study was to evaluate the role of Ang2 alone, or in combination with VEGF, in the acute phase of cerebral ischemia. The effect of these angiogenic factors on the ischemic lesion volume was evaluated by magnetic resonance imaging. We observed that timely administration of VEGF exacerbates ischemic damage. In contrast, Ang2 decreases the ischemic volume and this beneficial effect is maintained in the presence of VEGF. This investigation reports, for the first time, a protective role of Ang2 following cerebral ischemia, an action associated with a reduced BBB permeability. We propose that Ang2 represents a pertinent molecular target for the treatment of cerebral ischemia since acute brain damage may be limited by a pharmacological protection of the vascular compartment.

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