Penumbra in acute ischemic stroke

Acute ischemic stroke is one of the leading causes of disability and death worldwide. The brain tissue adjacent to the central necrotic core was first defined as ischemic penumbra characterized by reduced cerebral blood flow (CBF) with electrical failure but maintained ionic homeostasis and transmembrane electrical potentials. Since then, the evolving concepts of the ischemic penumbra have been proposed based on energy metabolism, CBF thresholds and protein synthesis, which provide insight for the diagnosis and treatment of acute ischemic stroke. This paper summarizes the recent advances in the understanding of ischemic penumbra, from its discovery to the diagnosis methods based on imaging techniques and biomarkers, finally some of the treatments developed. In addition, we discussed future perspectives on therapeutic targets beyond ischemic penumbra to develop a treatment for acute ischemic stroke.

Co-optimization Learning Network for MRI Segmentation of Ischemic Penumbra Tissues

Convolutional neural networks (CNNs) have brought hope for the medical image auxiliary diagnosis. However, the shortfall of labeled medical image data is the bottleneck that limits the performance improvement of supervised CNN methods. In addition, annotating a large number of labeled medical image data is often expensive and time-consuming. In this study, we propose a co-optimization learning network (COL-Net) for Magnetic Resonance Imaging (MRI) segmentation of ischemic penumbra tissues. COL-Net base on the limited labeled samples and consists of an unsupervised reconstruction network (R), a supervised segmentation network (S), and a transfer block (T). The reconstruction network extracts the robust features from reconstructing pseudo unlabeled samples, which is the auxiliary branch of the segmentation network. The segmentation network is used to segment the target lesions under the limited labeled samples and the auxiliary of the reconstruction network. The transfer block is used to co-optimization the feature maps between the bottlenecks of the reconstruction network and segmentation network. We propose a mix loss function to optimize COL-Net. COL-Net is verified on the public ischemic penumbra segmentation challenge (SPES) with two dozen labeled samples. Results demonstrate that COL-Net has high predictive accuracy and generalization with the Dice coefficient of 0.79. The extended experiment also shows COL-Net outperforms most supervised segmentation methods. COL-Net is a meaningful attempt to alleviate the limited labeled sample problem in medical image segmentation.

The MRI of Jahi McMath and Its Implications for the Global Ischemic Penumbra Hypothesis

Jahi McMath was diagnosed brain dead on 12/12/2013 in strict accordance with both the pediatric and adult Guidelines, reinforced by 4 isoelectric electroencephalograms and a radionuclide scan showing intracranial circulatory arrest. Her magnetic resonance imaging scan 9 1/2 months later surprisingly showed gross integrity of cortex, basal ganglia, thalamus, and upper brainstem. The greatest damage was in the white matter, which was extensively demyelinated and cystic, and in the lower brainstem, most likely from partial herniation that resolved. The apparent integrity of gray matter and the ascending reticular activating system may have provided a potential structural basis for the reemergence of some limited brain functions, while the white matter and lower brainstem lesions would have caused severe motor disability, brainstem areflexia and apnea. The findings indicate that there could never have been a period of sustained intracranial circulatory arrest. Rather, at the time of brain death diagnosis, low blood flow below the detection threshold of the radionuclide scan was sufficient to maintain widespread neuronal viability, though insufficient to support synaptic function. Her case represents the first indirect confirmation of the reality and clinical relevance of global ischemic penumbra, hypothesized in 1999 as a generally unacknowledged and possibly common brain death mimic.

MSC 2021 Virtual E-Abstract

1. A Cluster-Randomised Controlled Trial Evaluating The Effectiveness Of Stroke Riskometer In Improving Stroke Risk Probability In Adults: A Preliminary Analysis.2. Ph-Weighted Amide Proton Transfer Magnetic Resonance Imaging (APT MRI) Better Delineates The Acidotic Ischemic Penumbra.

The Autophagy-Related Organelle Autophagoproteasome Is Suppressed within Ischemic Penumbra

The peri-infarct region, which surrounds the irreversible ischemic stroke area is named ischemic penumbra. This term emphasizes the borderline conditions for neurons placed within such a critical region. Area penumbra separates the ischemic core, where frank cell loss occurs, from the surrounding healthy brain tissue. Within such a brain region, nervous matter, and mostly neurons are impaired concerning metabolic conditions. The classic biochemical marker, which reliably marks area penumbra is the over-expression of the heat shock protein 70 (HSP70). However, other proteins related to cell clearing pathways are modified within area penumbra. Among these, autophagy proteins like LC3 increase in a way, which recapitulates Hsp70. In contrast, components, such as P20S, markedly decrease. Despite apparent discrepancies, the present study indicates remarkable overlapping between LC3 and P20S redistribution within area penumbra. In fact, the amount of both proteins is markedly reduced within vacuoles. Specifically, a massive loss of LC3 + P20S immuno-positive vacuoles (autophagoproteasomes) is reported here. This represents the most relevant sub-cellular alteration here described in cell clearing pathways within area penumbra. The functional significance of these findings remains to be determined and it will take a novel experimental stream to decipher the fine-tuning of such a phenomenon.

Aortic dissection diagnosed on stroke computed tomography protocol: a case report

Background Aortic dissection is one of the causes of stroke. Because cerebral infarction with aortic dissection is a contraindication to intravenous recombinant tissue plasminogen activator (rt-PA) therapy, exclusion of aortic dissection is necessary prior to its administration. However, imaging takes time to provide a diagnosis, possibly causing delays in surgical treatment. Case presentation A 65-year-old Japanese female patient was transported to the hospital for a suspected stroke, with back pain and left upper and lower extremity palsy which occurred while eating. Upon arrival at the hospital, the left lower limb paralysis had improved, but the left upper limb paralysis remained. Right back pain had also developed. A plain head computed tomography (CT) scan performed 110 minutes after onset showed no acute bleeding or infarction. Subsequent CT perfusion (CTP) showed acute perfusion disturbance in the right hemisphere without infarction, known as ischemic penumbra. The four-dimensional maximum-intensity projection image reconstructed from CTP showed a delayed enhancement at the right internal carotid and right middle cerebral arteries compared to the contralateral side, suggesting a proximal vascular lesion. Contrast helical CT from the neck to abdomen revealed an acute aortic dissection of Stanford type A with false lumen patency. The dissection extended to the proximal right common carotid artery. The patient underwent an emergency total arch replacement and open stent graft. After recovering well, the patient was ambulatory upon discharge from the hospital. The combination of plain head CT, CTP, and helical CT scan from the neck to abdomen enabled us to evaluate for stroke and aortic dissection within a short amount of time, allowing for early therapeutic intervention. Conclusions When acute stroke is suspected due to neurological deficits, plain head CT is the first choice for imaging diagnosis. The addition of cervical CT angiography can reliably exclude stroke due to aortic dissection. CTP can identify ischemic penumbra, which cannot be diagnosed by plain head CT or diffusion-weighted magnetic resonance imaging. These combined stroke CT protocols helped us avoid missing an aortic dissection.