1. State-of-the-Art Imaging of Acute Stroke

2. Goals of Acute Stroke Imaging

3. Role of CT in Acute Stroke Evaluation
The goal of CT imaging in a patient with acute stroke is:
Exclude hemorrhage
Differentiate between irreversibly affected brain tissue and reversibly impaired tissue (dead tissue versus tissue at risk)
Identify stenosis or occlusion of major extra- and intracranial arteries
In this way we can select patients who are candidates for thrombolytic therapy.

4. CT Early signs of ischemia
CT has the advantage of being available 24 hours a day and is the gold standard for hemorrhage.
Hemorrhage on MRI can be quite confusing.
On CT 60% of infarcts are seen within 3-6 hrs and virtually all are seen in 24 hours.
The overall sensitivity of CT to diagnose stroke is 64% and the specificity is 85%.

5. Hypo attenuating brain tissue
The reason we see ischemia on CT is that in ischemia cytotoxic edema develops as a result of failure of the ion-pumps. These fail due to an inadequate supply of ATP.
An increase of brain water content by 1% will result in a CT attenuation decrease of 2.5 HU.

6. Hypo attenuating brain tissue
Hypoattenuation on CT is highly specific for irreversible ischemic brain damage if it is detected within first 6 hours.
Patients who present with symptoms of stroke and who demonstrate hypodensity on CT within first six hours were proven to have larger infarct volumes, more severe symptoms, less favorable clinical courses and they even have a higher risk of hemorrhage.

7. Patient with hypoattenuating brain tissue in the right hemisphere
Patient with hypoattenuating brain tissue in the right hemisphere. The diagnosis is infarction, because of the location (vascular territory of MCA and because of the involvement of gray and white matter, which is also very typical for infarction.

8. Hypodensity and sulcal effacement (arrowheads) in the right MCA distribution

9. Insular Ribbon sign
This refers to hypodensity and swelling of the insular cortex.
It is a very indicative and subtle early CT-sign of infarction in the territory of the MCA.
This region is very sensitive to ischemia because it is the furthest removed from collateral flow.
It has to be differentiated from herpes encephalitis.
Loss of normal gray-matter density leading to loss of cortical ribbon/density hours after stroke onset.

10. The cortex of the left insular ribbon is not visualized (arrow).

11. Obscuration of the lentiform nucleus
Obscuration of the lentiform nucleus, also called blurred basal ganglia, is an important sign of infarction. It is seen in MCA infarction and is one of the earliest and most frequently seen signs. The basal ganglia are almost always involved in MCA-infarction.
Obscuration of the lentiform nucleus or blurred basal ganglia

12. Dense MCA sign This is a result of thrombus or embolus in the MCA.
A patient with a dense MCA sign.
On CT-angiography occlusion of the MCA is visible.

13. High density in the right MCA (arrowheads)
High density in the right MCA (arrowheads). Compare it with the normal left MCA (arrow).
In patients presenting with clinical deficit referable to the MCA, the hyperdense vessel sign is present 35-50% of the time. This sign indicates poor outcome and poor response to IV-TPA therapy.

14. Dense basilar artery (arrow)
Dense basilar artery (arrow). Compare this to the normal internal carotid artery (arrowhead).

15. CT Angiography
CTA is a widely available technique for assessment of both the intracranial and extracranial circulation.
Its utility in acute stroke lies in its capabilities for demonstrating thrombi within intracranial vessels and for evaluating the carotid and vertebral arteries in the neck.

16. (a) Unenhanced CT image in a patient with acute right hemiplegia shows hyperattenuation in a proximal segment of the left MCA (arrows). (b, c) Axial (b) and coronal (c) reformatted images from CTA show the apparent absence of the same vessel segment (arrows).
Figure 8a.  (a) Unenhanced CT image in a 72-year-old woman with acute right hemiplegia shows hyperattenuation in a proximal segment of the left MCA (arrows). (b, c) Axial (b) and coronal (c) reformatted images from CT angiography show the apparent absence of the same vessel segment (arrows). The presence of an intravascular thrombus in this location was confirmed by comparing the reformatted images with the CT source images (not shown).

17. Significance of a Penumbra
Schematic of brain involvement in acute stroke shows a core of irreversibly infarcted tissue surrounded by a peripheral region of ischemic but salvageable tissue referred to as a penumbra. Without early recanalization, the infarction gradually expands to include the penumbra

18. Penumbra: Occlusion of the MCA with irreversibly affected or dead tissue in black and tissue at risk or penumbra in red.

19. Diagram shows the evolution of events at a microscopic level with decreasing cerebral perfusion (from right to left). Irreversible cell death generally occurs when cerebral blood flow decreases to less than 10 mL/100 g/min
Figure 1b.  (a) Schematic of brain involvement in acute stroke shows a core of irreversibly infarcted tissue surrounded by a peripheral region of ischemic but salvageable tissue referred to as a penumbra. Without early recanalization, the infarction gradually expands to include the penumbra. (b) Diagram shows the evolution of events at a microscopic level with decreasing cerebral perfusion (from right to left). Irreversible cell death generally occurs when cerebral blood flow decreases to less than 10 mL/100 g/min.

20. Occlusion of a major cerebral artery such as the proximal right MCA, illustrated here, results in changes in the hemodynamics of the brain that vary from patient to patient. With occlusion, collateral vascular channels can provide blood flow to ischemic regions. Here, collateral circulation from the right ACA distribution to the right MCA territory is depicted. The perfusion within the vascular territory of the occluded artery varies with some areas receiving little blood flow, whereas other areas receive near-normal amounts of blood flow. This results in 2 regions: an infarction core that represents irreversibly injured brain and an ischemic penumbra that may be clinically symptomatic but can be rescued if blood flow is restored.
The ischemic penumbra

21. A penumbra can be evaluated both on CT images (on which it is evidenced by a discrepancy in perfusion parameters) and on MRI (on which it is indicated by a mismatch between diffusion and perfusion parameters).
The presence of a penumbra has important implications for selection of the appropriate therapy and prediction of the clinical outcome. Intravenous thrombolytic treatment is not typically administered to patients with acute stroke beyond the conventional 4.5-hour period after the onset of symptoms, because such treatment results in an increased risk of hemorrhage.
The results of recent studies have demonstrated that IA thrombolytic therapy may benefit patients who are carefully selected according to findings of a diffusion or perfusion mismatch or a penumbra at imaging.

22. CT Perfusion Imaging
The clinical application of CT perfusion imaging in acute stroke is based on the hypothesis that the penumbra shows:
either (a) increased mean transit time with moderately decreased cerebral blood flow (>60%) and normal or increased cerebral blood volume (80%–100% or higher) secondary to autoregulatory mechanisms.
or (b) increased mean transit time with markedly reduced cerebral blood flow (>30%) and moderately reduced cerebral blood volume (>60%), whereas infarcted tissue shows severely decreased cerebral blood flow (<30%) and cerebral blood volume (<40%) with increased mean transit time.

23. A B
CT perfusion maps of cerebral blood volume (a) and cerebral blood flow (b) show, in the left hemisphere, a region of decreased blood volume (white oval) that corresponds to the ischemic core and a larger region of decreased blood flow (black oval in b) that includes the ischemic core and a peripheral region of salvageable tissue. The difference between the two maps (black oval = white oval) is the penumbra.

24. C A B
Acute stroke in a 65-year-old man with left hemiparesis. CT perfusion maps of cerebral blood volume (a), cerebral blood flow (b), and mean transit time (c) show mismatched abnormalities (arrows) that imply the presence of a penumbra. The area with decreased blood volume represents the ischemic core, and that with normal blood volume but decreased blood flow and increased mean transit time is the penumbra.

25. Role of MR Imaging in Acute Stroke Evaluation

26. Diffusion-weighted imaging
DWI is sensitive to the microscopic random motion of the water molecule protons, a value known as the apparent diffusion coefficient (ADC), which is measured and captured by this type of imaging.
The water molecules move in the direction of the magnetic field gradient; they accumulate a phase shift in their transverse magnetization relative to that of a stationary one, and this phase shift is directly related to the signal attenuation of the image.

27. Diffusion-weighted imaging
ADCs in ischemic areas are lower by 50% or more than those of normal brain areas, and they appear as bright areas (ie, hyperintensities) on the DWI.
Changes in the ADC occur as early as 10 minutes following onset of ischemia.

28. MRI in acute stroke. Left: Diffusion-weighted MRI in acute ischemic stroke performed 35 minutes after symptom onset. Right: Apparent diffusion coefficient (ADC) map obtained from the same patient at the same time.

29. ADC
Cytotoxic edema appears following sodium/potassium pump failure, which results from energy metabolism failure due to ischemic insult; this occurs within minutes of the onset of ischemia and produces an increase in brain tissue water of up to 3-5%.
Reduction in intracellular and extracellular water molecule movement is the presumed explanation for the drop in ADC values.

30. ADC
The acute drop in ADC is gradually normalized to baseline at 5-10 days after ischemia (pseudonormalization).
It even exceeds normal levels as time passes, helping in some cases to differentiate between acute, subacute, and chronic lesions.

31. Graph of mean rADC against region.

32. Conclusion
Apparent diffusion coefficient maps might assist clinicians in selecting patients with salvageable tissue within the ischemic penumbra.
Regions of the penumbra with rADC values greater than 0.90 are unlikely to proceed to infarction.
The infarct core typically has an rADC of less than 0.75.
Regions of the penumbra with intermediate rADC values are those at greatest risk of infarction.

33. DWI
DWI is very sensitive and relatively specific in detecting acute ischemic stroke.
DWI findings have shown high levels of diagnostic accuracy; however, small brainstem lacunar infarctions may escape detection.
Normal DWI in patients with strokelike symptoms should trigger further investigation for a nonischemic cause of the symptoms.
DWI has been shown to reveal diffusion abnormalities in almost 50% of patients with clinically defined transient ischemic attacks (TIAs).
It tends to be of higher yield at increasing time intervals from the onset of stroke symptoms.

34. Plot of the relationship between TIA symptom duration and presence of TIA-related lesions on diffusion-weighted images.A significant statistical correlation existed between symptom duration and presence of TIA-related lesions (P = .025); the significance was lost when only patients with symptoms lasting less than 6 hours were included in the analysis (P = .513).
Plot of the relationship between TIA symptom duration and presence of TIA-related lesions on DWI. A significant statistical correlation existed between symptom duration and presence of TIA-related lesions (P = .025); the significance was lost when only patients with symptoms lasting less than 6 hours were included in the analysis (P = .513).

35. Signal intensities on T2WI and DWI in time
In the acute phase T2WI will be normal.
The hyperintensity on T2WI reaches its maximum between 7 and 30 days.
DWI is already positive in the acute phase and then becomes more bright with a maximum at 7 days.
DWI in brain infarction will be positive for approximately for 3 weeks after onset (in spinal cord infarction DWI is only positive for one week!).
ADC will be of low signal intensity with a maximum at 24 hours and then will increase in signal intensity and finally becomes bright in the chronic stage.
Signal intensities on T2WI and DWI in time

37. False-negative Diffusion-weighted MR Findings in Acute Ischemic Stroke
DWI has been shown to be an excellent tool for the detection of acute stroke.
The rate of negative DWI studies in patients with acute ischemic stroke is highly variable, however, ranging from 0% to 21%.

38. Case 4: 74-year-old man with sudden left paresthesia
Case 4: 74-year-old man with sudden left paresthesia. A–D, Seven hours after the onset of symptoms, FLAIR image (10002/148/1, TI = 2200) (A) shows multiple diffuse areas of periventricular hyperintensity with a small hyperintensity in the right subthalamic area (arrowhead, A and C), whereas DWI (2825/92.6/1) (B) is considered normal. Forty-eight hours after symptom onset, FLAIR image remains unchanged (C) while DWI shows a clear hyperintensity in the right subthalamic area (D), matching clinical presentation.
74-year-old man with sudden left paresthesia. A–D, Seven hours after the onset of symptoms, FLAIR image (A) shows multiple diffuse areas of periventricular hyperintensity with a small hyperintensity in the right subthalamic area (arrowhead, A and C), whereas DWI (B) is considered normal. Forty-eight hours after symptom onset, FLAIR image remains unchanged (C) while DWI shows a clear hyperintensity in the right subthalamic area (D), matching clinical presentation.

39. Case 6: 61-year-old man with sudden right crural hemiparesis
Case 6: 61-year-old man with sudden right crural hemiparesis. A–D, Twenty-two hours after onset of symptoms, FLAIR image (10002/148/1, TI = 2200) (A) shows a small cortical hyperintensity in the left paracentral lobule (arrowhead, A and C), whereas DWI (2825/92.6/1) (B) fails to show a stroke lesion. Four days later, the lesion is still visible on FLAIR image (C), and DWI (D) displays a hyperintensity in the paracentral lobule, consistent with a recent stroke lesion and matching clinical presentation.
61-year-old man with sudden right crural hemiparesis. A–D, Twenty-two hours after onset of symptoms, FLAIR image (A) shows a small cortical hyperintensity in the left paracentral lobule (arrowhead, A and C), whereas DWI (B) fails to show a stroke lesion. Four days later, the lesion is still visible on FLAIR image (C), and DWI (D) displays a hyperintensity in the paracentral lobule, consistent with a recent stroke lesion and matching clinical presentation.

40. Case 7: 45-year-old man with sudden onset of vertigo, dysmetria, and somnolence. A–D, On initial MR examination, performed 5.5 hours after onset, MR angiogram (not shown) displayed a partially thrombosed dolichobasilar artery, which was responsible for the mass effect on the brain stem and heterogeneous signal anterior to the pons on FLAIR images. Initial FLAIR image (A) (10002/148/1, TI = 2200) and DWI (B) fail to reveal a stroke lesion. On follow-up MR examination, performed 15 hours after onset, FLAIR image shows a small right-sided brain stem hyperintensity (arrowhead) (C), which is more clearly visible on DWI (D).
45-year-old man with sudden onset of vertigo, dysmetria, and somnolence. A–D, On initial MR examination, performed 5.5 hours after onset. Initial FLAIR image (A) and DWI (B) fail to reveal a stroke lesion. On follow-up MR examination, performed 15 hours after onset, FLAIR image shows a small right-sided brain stem hyperintensity (arrowhead) (C), which is more clearly visible on DWI (D).

41. Estimation of the probability of false-negative DWI findings by means of a logistic regression. The probability of false-negative DWI findings is plotted against time for stroke lesions located in the anterior (circles) and posterior (crosses) circulation. For vertebrobasilar stroke lesions (crosses), the probability of false-negative DWI findings diminishes when MR latency increases (𝛉 = 0.438, β = 0.127, P = .04). For lesions located in the anterior circulation (circles), this relation is no longer significant

42. Conclusion
False-negative DWI studies can occur during the first 24 hours of a stroke; that negative DWI findings obtained in the first 24 hours after onset are not a reliable indicator by which to rule out a stroke lesion, especially if symptoms are suggestive of a stroke in the posterior circulation; and that false-negative DWI findings are no longer observed after 24 hours.
The diagnosis of stroke should not be ruled out on the basis of early negative DWI studies. Moreover, DWI should be repeated more than 24 hours after onset in the event of a negative initial DWI study in a patient with long-lasting clinical symptoms consistent with ischemic stroke.

43. Perfusion-weighted imaging
With this technique, information about the perfusion status of the brain is available. The most commonly used technique is bolus-contrast tracking. The imaging is based on the monitoring of a nondiffusible contrast material (gadolinium) passing through brain tissue.
The signal intensity declines as contrast material passes through the infarcted area and returns to normal as it exits this area. A curve is derived from this tracing data (ie, signal washout curve), which represents and estimates the cerebral blood volume (CBV).

44. Magnetic resonance imaging in acute stroke
Magnetic resonance imaging in acute stroke. Left: Perfusion-weighted MRI of a patient who presented 1 hour after onset of stroke symptoms. Right: Mean transfer time (MTT) map of the same patient.

45. Perfusion-weighted imaging
DWI and PWI together have been shown to be superior to conventional MRI both in early phases and also up to 48 hours after the onset of stroke.
Using both DWI and PWI is very important because together they provide information about location and extent of infarction within minutes of onset; when performed in series, they can provide information about the pattern of evolution of the ischemic lesion.
This information may be of great importance in choosing the appropriate treatment modality as well as in predicting outcome and prognosis.

46. The diffusion-perfusion mismatch, ie, the difference in size between lesions captured by DWI and PWI, usually represents the ischemic penumbra, which is the region of incomplete ischemia that lies next to the core of the infarction.
The ischemic penumbra is regarded as an area that is viable but under ischemic threat; it can be saved if appropriate intervention is promptly instituted.
The viability of this region could extend up to 48 hours after the onset of stroke.

47. Diffusion-perfusion mismatch in acute ischemic stroke
Diffusion-perfusion mismatch in acute ischemic stroke. The perfusion abnormality (right) is larger than the diffusion abnormality (left), indicating the ischemic penumbra, which is at risk of infarction.

48. Diffusion in yellow. Perfusion in red. Mismatch in blue is penumbra.

49. A patient with sudden onset of neurological symptoms
A patient with sudden onset of neurological symptoms. MR was performed 1 hour after onset of symptoms. These images are normal.
On the DWI there is a large area with restricted diffusion in the territory of the right MCA Notice also the involvement of the basal ganglia. There is a perfect match with the perfusion images, so this patient should not undergo any form of IA thrombolytic therapy.

50. It is clearly visible on CT (i. e. irreversible changes)
It is clearly visible on CT (i.e. irreversible changes). There is a match of DWI and Perfusion, so no IA therapy.

51. The DWI and ADC map is shown.
Almost the whole left cerebral hemisphere is at risk due to hypoperfusion. This patient is an ideal candidate for therapy.

52. MR Angiography
Like CT angiography, MRA is useful for detecting intravascular occlusion due to a thrombus and for evaluating the carotid bifurcation in patients with acute stroke.
Time-of-flight MRA and contrast-enhanced MR angiography are commonly used to evaluate the intracranial and extracranial circulation.

53. Figure 13a. Intravascular thrombus
Figure 13a.  Intravascular thrombus. Time-of-flight MR angiograms in two patients with acute stroke symptoms reveal flow gaps in the left proximal middle cerebral artery (arrow in a) and the basilar artery (arrows in b). Both findings were due to intravascular thrombi, which were confirmed later at digital subtraction angiography. (Courtesy of Ellen Hoeffner, MD, University of Michigan Health System, Ann Arbor, Michigan.)‏
Time-of-flight MRA in two patients with acute stroke symptoms reveal flow gaps in the left proximal middle cerebral artery (arrow in a) and the basilar artery (arrows in b). Both findings were due to intravascular thrombi, which were confirmed later at DSA.

54. Patient Limitations   CTA MRA
Pacemaker, Implantable Stimulator, *** --
Certain Aneurysm Clips
Endoluminal Stents/ Surgical Clips *** *
At Anastomoses 
Claustrophobia   *** *
Difficulty with Breath Holding *** *
Moderate to Severe Allergy to * ***
Iodinated Contrast
Time of Examination min min

55. MRA: Strengths Safety Versatility Proven efficacy
The ability of the study to obtain information beyond anatomy
Ease of data post processing

56. MRA: Weaknesses inability to see calcium
turbulent flow and in plane flow causing apparent exaggerated stenosis
speed that requires long breath holds for some diagnoses
degree of complexity
contraindications to MRA
artifacts
long acquisition and reconstruction times
limited spatial resolution.

57. CTA: Strengths
CTA is faster, less expensive, more widely available, more sensitive for mural calcium, can display bony landmarks well and also can be used in patients with aneurysm clips and other MR incompatible metallic hardware.
CTA images are dependent on the volume of blood within the vessel as compared to MRA where the image production is dependent on the velocity of blood in the vessel.

58. CTA: Weaknesses use of intravenous contrast and radiation exposure.
catheter angiography provides better spatial and temporal resolution in comparison to CTA.

59. Technique Selection for the Evaluation of Acute Stroke with CT and MRI

60. Comparison of CT and MR Imaging for Evaluation of Acute Stroke

62. Suggested imaging protocols for patients presenting with acute stroke symptoms based on the clinical scenario and the therapeutic options considered and available
Suggested imaging protocols for patients presenting with acute stroke symptoms based on the clinical scenario and the therapeutic options considered and available. Each of the gray boxes represents 1 imaging strategy. In order not to delay treatment, a standardized imaging approach should be used: One imaging strategy (gray box) should be selected, and all imaging studies belonging to this strategy should be performed upfront in as few sessions as possible: To assess the etiology of the intracranial hemorrhage (CTA for vascular pathologies, such as aneurysms, arteriovenous malformations, vasculopathies; MR imaging for vascular malformations, neoplastic and other pathologies associated with hemorrhage). Also if the patient is not a candidate for IV tPA (contraindication to tPA, outside the time window for tPA) or if IV tPA failed or it is thought that it may fail. For patients who are outside the time window for acute reperfusion therapies (>4.5 hours at sites where only IV tPA is being considered; >8 hours at sites where endovascular therapy is considered) and for patients with TIAs, emphasis is on secondary prevention and their imaging work-up should be focused on vascular imaging (CTA, MRA or Doppler-ultrasound [DUS]) to assess carotid arteries as a possible cause of the ischemic stroke, with secondary prevention in mind. If MRA is obtained, it makes sense to concurrently obtain MR imaging with DWI, FLAIR, and GRE/SWI. Echocardiography should also be obtained to assess for cardiac sources. If available, MR imaging/MRA is the preferred imaging technique for TIA patients. At institutions where MR imaging is available 24/7 and can be performed within a short time after admission. To assess for intracranial hemorrhage. To assess the extent of ischemic core. To assess the location and extent of the intravascular clot. To assess carotid atherosclerotic disease. To assess the extent of viable tissue.