Section 1: Non-Contrast CT, DWI/ADC, and the WAKE-UP Mismatch

~1:46 – Non-Contrast CT, DWI/ADC, and the WAKE-UP Mismatch

Bottom line: the non-contrast head CT exists to answer one binary question (is there blood?) because tissue plasminogen activator (alteplase) is permanently off the table if hemorrhage is present; bright on DWI plus dark on ADC is the non-negotiable signature of acute ischemia, and a positive DWI with a negative fluid-attenuated inversion recovery (FLAIR) is the WAKE-UP tissue clock that places onset under 4.5 hours.

The non-contrast head CT is the first imaging study in suspected acute ischemic stroke, but its purpose is frequently misframed by trainees. The scan is not designed to confirm ischemia. Ischemia may be invisible on CT for the first 6 to 12 hours. The scan is designed to exclude hemorrhage, because that single binary answer drives the entire reperfusion algorithm. If blood is present, alteplase is absolutely contraindicated. If no blood is present, the patient may proceed to intravenous thrombolysis, mechanical thrombectomy, or both. Acute hemorrhage shows up immediately as a glaring hyperdensity because circulating blood that has escaped the vascular space coagulates rapidly, and the protein density of clotted blood attenuates the X-ray beam dramatically.

When subtle early ischemic changes are present on non-contrast CT, an experienced reader can sometimes identify them. Loss of gray-white matter differentiation occurs because cytotoxic edema in the cortex blurs the normally distinct boundary between gray and white matter, classically appearing in the insular cortex as the insular ribbon sign or along the lateral margin of the lentiform nucleus. Sulcal effacement reflects swollen tissue compressing the cerebrospinal-fluid-filled sulci. The hyperdense MCA sign is a bright dense focus within the middle cerebral artery itself, representing acute thrombus packed with red cells and fibrin within the vessel lumen. The presence of these signs supports the clinical diagnosis, but their absence does not change the algorithm. The CT was obtained to rule out blood, and if blood is absent, the team proceeds to determine reperfusion candidacy.

Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) is far more sensitive and detects ischemia within 3 to 30 minutes of symptom onset. The physics matters because boards test the cellular link directly. When neurons become ischemic, the sodium-potassium adenosine triphosphatase (ATPase) pump fails, sodium and water flood into the cell, and cytotoxic edema swells the membrane outward. Water molecules that normally diffuse freely through the extracellular space become trapped inside the swollen cell. DWI is tuned to detect this restricted Brownian motion, and trapped water lights up bright on the DWI image.

A bright DWI signal alone is not enough to confirm acute ischemia, however, and this is where the apparent diffusion coefficient (ADC) map becomes essential. DWI sequences inherently sit on top of T2-weighted contrast, and any chronic lesion containing fluid-filled encephalomalacia from an old stroke will appear bright on the underlying T2, then shine through into the DWI image as a false positive. This artifact is called T2 shine-through. The ADC map mathematically removes the T2 contribution and displays only the diffusion information. True acute restricted diffusion appears dark on the ADC map; T2 shine-through appears bright. The board-critical rule is the two-step verification: bright on DWI AND dark on ADC equals acute ischemic infarction. Bright on DWI plus bright on ADC equals T2 shine-through and is a chronic finding, not an acute emergency.

The DWI-FLAIR mismatch extends this principle into a tissue clock. Fluid-attenuated inversion recovery (FLAIR) suppresses cerebrospinal fluid signal and is sensitive to vasogenic edema, the extracellular fluid that accumulates only after the blood-brain barrier breaks down. Vasogenic edema requires inflammatory cytokines, vascular endothelial growth factor, and matrix metalloproteinases to degrade the tight junctions between cerebral endothelial cells, and that cascade takes time. DWI lights up within minutes; FLAIR does not become bright until roughly 4.5 to 6 hours after symptom onset. A patient with a bright DWI lesion and a normal FLAIR in the same territory has a stroke that is likely under 4.5 hours old, regardless of the clock on the wall. This DWI-FLAIR mismatch was the imaging selection criterion for the WAKE-UP trial, which proved that patients with unknown onset time (the classic wake-up stroke patient who goes to bed intact and awakens hemiplegic) could safely receive intravenous alteplase when their imaging confirmed recent ischemia. The trial completed the paradigm shift from clock-based to tissue-based eligibility.