Background: In stroke due to middle cerebral artery (MCA) occlusion, collaterals may sustain tissue in the peripheral MCA territory, extending the time window for recanalizing therapies. However, MCA occlusions often block some or all of the ‘lenticulostriate’ (LS) arteries originating from the M1 segment, eliminating blood flow to dependent territories in the striatum, which have no collateral supply. This study examines whether mechanical thrombectomy (MTE) can avert imminent striatal infarction in patients with acute MCA occlusion. Methods: 279 patients with isolated MCA occlusion subjected to MTE were included. Actual LS occlusions and infarctions were assigned to predefined ‘LS occlusion’ and ‘LS infarct’ patterns derived from known LS vascular anatomy. The predictive performance of LS occlusion patterns regarding ensuing infarction in striatal subterritories was assessed by standard statistical measures. Results: LS occlusion patterns predicted infarction in associated striatal subterritories with a positive predictive value (PPV) of 91% and a negative predictive value of 81%. In 15 of the 22 patients who did not develop the predicted striatal infarctions, reassessment of angiographies revealed LS vascular supply variants that explained these ‘false positive’ LS occlusion patterns, raising the PPV to 96%. Symptom onset to recanalization times were relatively short, but this alone could not account for the false positive LS occlusion patterns in the remaining seven of these patients. Conclusions: With currently achievable symptom onset to recanalization times, striatal infarctions are determined by MCA occlusion sites and individual vascular anatomy, and cannot normally be averted by MTE, but there are exceptions. Further study of such exceptional cases may yield important insights into the determinants of infarct growth in the hyperacute phase of infarct evolution.

The RIG-I-like helicase melanoma differentiation-associated protein 5 (MDA5) is an innate immune receptor for double-stranded viral RNA (dsRNA) that, upon activation, induces a Type I interferon (IFN)-driven immune response. In the present study, we demonstrate that human und murine pancreatic cancer cells express functional MDA5 and are highly sensitive to MDA5-induced cell death. Activation of MDA5 by cytosolic delivery of the synthetic dsRNA analog poly(I:C) led to phosphorylation of the transcription factor IRF3, IFNβ production and upregulation of MHC-I expression. MDA5 signaling also induced tumor cell apoptosis via the intrinsic pathway and sensitized tumor cells toward extrinsic, Fas-mediated apoptosis. Systemic treatment of orthotopic pancreatic cancer-bearing mice with the MDA5 ligand resulted in activated CD8⁺ T cell tumor infiltration, an increased frequency of tumor antigen-specific CD8⁺ T cells and an immunogenic cytokine milieu in the tumor microenvironment. These effects were paralleled by MDA5-induced pronounced tumor cell death in situ and significantly prolonged survival in two different mouse models for pancreatic cancer, an immunotherapeutic response dependent on CD8⁺ T cells. Treated mice were further protected from subsequent tumor challenge. In summary, we identified MDA5 as a novel therapeutic target for overcoming apoptosis resistance and tumor-mediated immunosuppression in pancreatic cancer. MDA5 ligands link innate with adaptive immune mechanisms for effective tumor control.

Functional connectivity of blood oxygenation level dependent signal fluctuations (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence in neural population activity; however, as both neuronal and vascular-hemodynamic processes underlie BOLD signals, impaired perfusion might also contribute to reduced BOLD-FC; 42 AD patients and 27 controls underwent simultaneous PET/MR imaging. Resting-state functional MRI assessed BOLD co-activity to quantify BOLD-FC, pulsed arterial spin labeling (pASL) assessed cerebral blood flow (CBF) as proxy for vascular hemodynamics, and ¹⁸F-fluorodeoxyglucose PET assessed glucose metabolism (GluMet) to index neuronal activity. Patients’ BOLD-FC, CBF, and GluMet were reduced within the same precuneal parietal regions. BOLD-FC was positively associated with mean CBF, specifically in patients and controlled for GluMet levels, suggesting that BOLD-FC reductions correlate with pASL-derived hypoperfusion in AD, independently from ¹⁸F-fluorodeoxyglucose PET-derived hypometabolism. Data indicate that impaired vascular hemodynamic processes contribute to reduced BOLD connectivity in AD.

To evaluate the impact of a novel, deep-learning-based image reconstruction (DLIR) algorithm on image quality in CT angiography of the aorta, we retrospectively analyzed 51 consecutive patients who underwent ECG-gated chest CT angiography and non-gated acquisition for the abdomen on a 256-dectector-row CT. Images were reconstructed with adaptive statistical iterative reconstruction (ASIR-V) and DLIR. Intravascular image noise, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) were quantified for the ascending aorta, the descending thoracic aorta, the abdominal aorta and the iliac arteries. Two readers scored subjective image quality on a five-point scale. Compared to ASIR-V, DLIR reduced the median image noise by 51–54% for the ascending aorta and the descending thoracic aorta. Correspondingly, median CNR roughly doubled for the ascending aorta and descending thoracic aorta. There was a 38% reduction in image noise for the abdominal aorta and the iliac arteries, with a corresponding improvement in CNR. Median subjective image quality improved from good to excellent at all anatomical levels. In CT angiography of the aorta, DLIR substantially improved objective and subjective image quality beyond what can be achieved by state-of-the-art iterative reconstruction. This can pave the way for further radiation or contrast dose reductions.